The composition of the cellular proteome is under the control of multiple processes, one of the most important being translation initiation. The majority of eukaryotic cellular mRNAs initiates translation by the cap-dependent or scanning mode of translation initiation, a mechanism that depends on the recognition of the m7G(5′)ppp(5′)N, known as the cap. However, mRNAs encoding proteins required for cell survival under stress bypass conditions inhibitory to cap-dependent translation; these mRNAs often harbor internal ribosome entry site (IRES) elements in their 5′UTRs that mediate internal initiation of translation. This mechanism is also exploited by mRNAs expressed from the genome of viruses infecting eukaryotic cells. In this paper we discuss recent advances in understanding alternative ways to initiate translation across eukaryotic organisms. 1. Alternative Translation Initiation Mechanisms: An Important Layer of Gene Expression Control The coding capacity of eukaryotic genomes is much larger than anticipated. Many layers of gene expression control operate at the posttranscriptional level, as illustrated by the RNA splicing process, the noncoding RNAs regulatory elements, and the large repertoire of factors that contribute to control mRNA transport, localization, stability, and translation. Translation control is one of the posttranscriptional cellular processes that exert a profound impact on the composition of the cellular proteome. This is particularly relevant to maintain homeostasis in response to stress induced by a large variety of environmental factors, as well as during development or disease [1]. In addition, these layers of gene expression control contribute to increase the coding capacity of the genome by generating different polypeptides from the same transcriptional unit. The majority of cellular mRNAs initiate translation by a mechanism that depends on the recognition of the m7G(5′)ppp(5′)N structure (termed cap) located at the 5′end of most mRNAs (Figure 1(a)). This manner of initiating translation involves a large number of auxiliary proteins termed eukaryotic initiation factors (eIFs) [1]. The 5′cap structure is recognized by eIF4E that, in turn, is bound to the scaffold protein eIF4G and the RNA helicase eIF4A (within a trimeric complex termed eIF4F). Additionally, eIF4G further interacts with eIF3 and the poly(A)-binding protein (PABP) that is bound to the poly(A) tail of the mRNA. Separately, the 40S ribosomal subunit associates with the ternary complex (TC) consisting of the initiator methionyl-tRNAi and eIF2-GTP, leading to the
References
[1]
N. Sonenberg and A. G. Hinnebusch, “Regulation of translation initiation in eukaryotes: mechanisms and biological targets,” Cell, vol. 136, no. 4, pp. 731–745, 2009.
[2]
K. A. Spriggs, M. Bushell, and A. E. Willis, “Translational regulation of gene expression during conditions of cell stress,” Molecular Cell, vol. 40, no. 2, pp. 228–237, 2010.
[3]
F. Martin, S. Barends, S. Jaeger, L. Schaeffer, L. Prongidi-Fix, and G. Eriani, “Cap-assisted internal initiation of translation of histone H4,” Molecular Cell, vol. 41, pp. 197–209, 2011.
[4]
Z. Wang, M. Parisien, K. Scheets, and W. A. Miller, “The cap-binding translation initiation factor, eIF4E, binds a pseudoknot in a viral cap-independent translation element,” Structure, vol. 19, pp. 868–880, 2011.
[5]
C. Hernandez-Sanchez, A. Mansilla, E. J. de la Rosa, G. E. Pollerberg, E. Martínez-Salas, and F. de Pablo, “Upstream AUGs in embryonic proinsulin mRNA control its low translation level,” The EMBO Journal, vol. 22, no. 20, pp. 5582–5592, 2003.
[6]
L. Blaszczyk and J. Ciesiolka, “Secondary structure and the role in translation initiation of the 5′-terminal region of p53 mRNA,” Biochemistry, vol. 50, pp. 7080–7092, 2011.
[7]
A. M. Rakotondrafara, C. Polacek, E. Harris, and W. A. Miller, “Oscillating kissing stem-loop interactions mediate 5′ scanning-dependent translation by a viral 3′-cap-independent translation element,” RNA, vol. 12, no. 10, pp. 1893–1906, 2006.
[8]
I. R. Powley, A. Kondrashov, L. A. Young et al., “Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes,” Genes and Development, vol. 23, no. 10, pp. 1207–1220, 2009.
[9]
K. Babinger, A. Hallmann, and R. Schmitt, “Translational control of regA, a key gene controlling cell differentiation in Volvox carteri,” Development, vol. 133, no. 20, pp. 4045–4051, 2006.
[10]
I. P. Ivanov, J. F. Atkins, and A. J. Michael, “A profusion of upstream open reading frame mechanisms in polyamine-responsive translational regulation,” Nucleic Acids Research, vol. 38, no. 2, pp. 353–359, 2009.
[11]
V. A. Stupina, X. Yuan, A. Meskauskas, J. D. Dinman, and A. E. Simon, “Ribosome binding to a 5′ translational enhancer is altered in the presence of the 3′ untranslated region in cap-independent translation of turnip crinkle virus,” Journal of Virology, vol. 85, pp. 4638–4653, 2011.
[12]
X. Yuan, K. Shi, A. Meskauskas, and A. E. Simon, “The 3′ end of Turnip crinkle virus contains a highly interactive structure including a translational enhancer that is disrupted by binding to the RNA-dependent RNA polymerase,” RNA, vol. 15, no. 10, pp. 1849–1864, 2009.
[13]
E. Martínez-Salas, “The impact of RNA structure on picornavirus IRES activity,” Trends in Microbiology, vol. 16, no. 5, pp. 230–237, 2008.
[14]
A. A. Komar and M. Hatzoglou, “Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states,” Cell Cycle, vol. 10, pp. 229–240, 2011.
[15]
J. Pelletier and N. Sonenberg, “Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA,” Nature, vol. 334, no. 6180, pp. 320–325, 1988.
[16]
S. K. Jang, H. G. Krausslich, M. J. H. Nicklin, G. M. Duke, A. C. Palmenberg, and E. Wimmer, “A segment of the 5′ nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation,” Journal of Virology, vol. 62, no. 8, pp. 2636–2643, 1988.
[17]
E. Martinez-Salas, J. C. Saiz, M. Davila, G. J. Belsham, and E. Domingo, “A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo,” Journal of Virology, vol. 67, no. 7, pp. 3748–3755, 1993.
[18]
A. V. Pisarev, L. S. Chard, Y. Kaku, H. L. Johns, I. N. Shatsky, and G. J. Belsham, “Functional and structural similarities between the internal ribosome entry sites of hepatitis C virus and porcine teschovirus, a picornavirus,” Journal of Virology, vol. 78, no. 9, pp. 4487–4497, 2004.
[19]
Y. Yu, T. R. Sweeney, P. Kafasla, R. J. Jackson, T. V. Pestova, and C. U. Hellen, “The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES,” The EMBO Journal, vol. 30, pp. 4423–4436, 2011.
[20]
M. M. Willcocks, N. Locker, Z. Gomwalk, et al., “Structural features of the Seneca valley virus internal ribosome entry site (IRES) element: a picornavirus with a pestivirus-like IRES,” Journal of Virology, vol. 85, pp. 4452–4461, 2011.
[21]
M. Honda, L. H. Ping, R. C. A. Rijnbrand et al., “Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA,” Virology, vol. 222, no. 1, pp. 31–42, 1996.
[22]
R. Rijnbrand, T. van der Straaten, P. A. van Rijn, W. J. M. Spaan, and P. J. Bredenbeek, “Internal entry of ribosomes is directed by the 5′ noncoding region of classical swine fever virus and is dependent on the presence of an RNA pseudoknot upstream of the initiation codon,” Journal of Virology, vol. 71, no. 1, pp. 451–457, 1997.
[23]
N. Locker, N. Chamond, and B. Sargueil, “A conserved structure within the HIV gag open reading frame that controls translation initiation directly recruits the 40S subunit and eIF3,” Nucleic Acids Research, vol. 39, no. 6, pp. 2367–2377, 2011.
[24]
M. Vallejos, J. Deforges, T. D. Plank, et al., “Activity of the human immunodeficiency virus type 1 cell cycle-dependent internal ribosomal entry site is modulated by IRES trans-acting factors,” Nucleic Acids Research, vol. 39, pp. 6186–6200, 2011.
[25]
S. Vagner, A. Waysbort, M. Marenda, M. C. Gensac, F. Amalric, and A. C. Prats, “Alternative translation initiation of the Moloney murine leukemia virus mRNA controlled by internal ribosome entry involving the p57/PTB splicing factor,” The Journal of Biological Chemistry, vol. 270, no. 35, pp. 20376–20383, 1995.
[26]
V. Camerini, D. Decimo, L. Balvay et al., “A dormant internal ribosome entry site controls translation of feline immunodeficiency virus,” Journal of Virology, vol. 82, no. 7, pp. 3574–3583, 2008.
[27]
M. Vallejos, P. Ramdohr, F. Valiente-Echeverría et al., “The 5′-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation,” Nucleic Acids Research, vol. 38, no. 2, pp. 618–632, 2009.
[28]
K. E. Woolaway, K. Lazaridis, G. J. Belsham, M. J. Carter, and L. O. Roberts, “The 5′ untranslated region of Rhopalosiphum padi virus contains an internal ribosome entry site which functions efficiently in mammalian, plant, and insect translation systems,” Journal of Virology, vol. 75, no. 21, pp. 10244–10249, 2001.
[29]
J. E. Wilson, T. V. Pestova, C. U. T. Hellen, and P. Sarnow, “Initiation of protein synthesis from the A site of the ribosome,” Cell, vol. 102, no. 4, pp. 511–520, 2000.
[30]
A. E. Firth, Q. S. Wang, E. Jan, and J. F. Atkins, “Bioinformatic evidence for a stem-loop structure 5′-adjacent to the IGR-IRES and for an overlapping gene in the bee paralysis dicistroviruses,” Virology Journal, vol. 6, article 193, 2009.
[31]
J. Lu, Y. Hu, L. Hu et al., “Ectropis obliqua picorna-like virus IRES-driven internal initiation of translation in cell systems derived from different origins,” Journal of General Virology, vol. 88, no. 10, pp. 2834–2838, 2007.
[32]
N. Shibuya and N. Nakashima, “Characterization of the 5′ internal ribosome entry site of Plautia stali intestine virus,” Journal of General Virology, vol. 87, no. 12, pp. 3679–3686, 2006.
[33]
C. Czibener, D. Alvarez, E. Scodeller, and A. V. Gamarnik, “Characterization of internal ribosomal entry sites of Triatoma virus,” Journal of General Virology, vol. 86, no. 8, pp. 2275–2280, 2005.
[34]
A. Karetnikov and K. Lehto, “The RNA2 5′ leader of Blackcurrant reversion virus mediates efficient in vivo translation through an internal ribosomal entry site mechanism,” Journal of General Virology, vol. 88, pp. 286–297, 2007.
[35]
O. Fernandez-Miragall and C. Hernandez, “An internal ribosome entry site directs translation of the 3′-gene from pelargonium flower break virus genomic RNA: implications for infectivity,” PLoS ONE, vol. 6, article e22617, 2011.
[36]
Y. L. Dorokhov, P. A. Ivanov, T. V. Komarova, M. V. Skulachev, and J. G. Atabekov, “An internal ribosome entry site located upstream of the crucifer-infecting tobamovirus coat protein (CP) gene can be used for CP synthesis in vivo,” Journal of General Virology, vol. 87, no. 9, pp. 2693–2697, 2006.
[37]
H. M. Jaag, L. Kawchuk, W. Rohde, R. Fischer, N. Emans, and D. Prüfer, “An unusual internal ribosomal entry site of inverted symmetry directs expression of a potato leafroll polerovirus replication-associated protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8939–8944, 2003.
[38]
D. C. Y. Koh, S. M. Wong, and D. X. Liu, “Synergism of the 3′-untranslated region and an internal ribosome entry site differentially enhances the translation of a plant virus coat protein,” The Journal of Biological Chemistry, vol. 278, no. 23, pp. 20565–20573, 2003.
[39]
V. Zeenko and D. R. Gallie, “Cap-independent translation of tobacco etch virus is conferred by an RNA pseudoknot in the 5′-leader,” The Journal of Biological Chemistry, vol. 280, no. 29, pp. 26813–26824, 2005.
[40]
S. Garlapati and C. C. Wang, “Structural elements in the 5′-untranslated region of giardiavirus transcript essential for internal ribosome entry site-mediated translation initiation,” Eukaryotic Cell, vol. 4, no. 4, pp. 742–754, 2005.
[41]
J. A. Maga, G. Widmer, and J. H. LeBowitz, “Leishmania RNA virus 1-mediated cap-independent translation,” Molecular and Cellular Biology, vol. 15, no. 9, pp. 4884–4889, 1995.
[42]
L. Grainger, L. Cicchini, M. Rak et al., “Stress-inducible alternative translation initiation of human cytomegalovirus latency protein pUL138,” Journal of Virology, vol. 84, no. 18, pp. 9472–9486, 2010.
[43]
Y. Yu and J. C. Alwine, “19S late mRNAs of simian virus 40 have an internal ribosome entry site upstream of the virion structural protein 3 coding sequence,” Journal of Virology, vol. 80, no. 13, pp. 6553–6558, 2006.
[44]
A. Isaksson, M. Berggren, K. Ekeland-Sjoberg, T. Samuelsson, and A. Ricksten, “Cell specific internal translation efficiency of Epstein-Barr virus present in solid organ transplant patients,” Journal of Medical Virology, vol. 79, no. 5, pp. 573–581, 2007.
[45]
A. Tahiri-Alaoui, L. P. Smith, S. Baigent et al., “Identification of an intercistronic internal ribosome entry site in a Marek's disease virus immediate-early gene,” Journal of Virology, vol. 83, no. 11, pp. 5846–5853, 2009.
[46]
J. Fernandez, I. Yaman, C. Huang et al., “Ribosome stalling regulates ires-mediated translation in eukaryotes, a parallel to prokaryotic attenuation,” Molecular Cell, vol. 17, no. 3, pp. 405–416, 2005.
[47]
D. Q. Yang, M. J. Halaby, and Y. Zhang, “The identification of an internal ribosomal entry site in the 5′-untranslated region of p53 mRNA provides a novel mechanism for the regulation of its translation following DNA damage,” Oncogene, vol. 25, no. 33, pp. 4613–4619, 2006.
[48]
M. B. Al-Fageeh and C. M. Smales, “Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative mRNAs,” RNA, vol. 15, no. 6, pp. 1165–1176, 2009.
[49]
B. M. Pickering, S. A. Mitchell, K. A. Spriggs, M. Stoneley, and A. E. Willis, “Bag-1 internal ribosome entry segment activity is promoted by structural changes mediated by poly(rC) binding protein 1 and recruitment of polypyrimidine tract binding protein 1,” Molecular and Cellular Biology, vol. 24, no. 12, pp. 5595–5605, 2004.
[50]
B. Schepens, S. A. Tinton, Y. Bruynooghe, R. Beyaert, and S. Cornelis, “The polypyrimidine tract-binding protein stimulates HIF-1α IRES-mediated translation during hypoxia,” Nucleic Acids Research, vol. 33, no. 21, pp. 6884–6894, 2005.
[51]
D. G. Macejak and P. Sarnow, “Internal initiation of translation mediated by the 5′ leader of a cellular mRNA,” Nature, vol. 353, no. 6339, pp. 90–94, 1991.
[52]
M. Stoneley, T. Subkhankulova, J. P. C. Le Quesne et al., “Analysis of the c-myc IRES; A potential role for cell-type specific trans-acting factors and the nuclear compartment,” Nucleic Acids Research, vol. 28, no. 3, pp. 687–694, 2000.
[53]
S. Bonnal, C. Schaeffer, L. Créancier et al., “A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons,” The Journal of Biological Chemistry, vol. 278, no. 41, pp. 39330–39336, 2003.
[54]
J. T. Fox, W. K. Shin, M. A. Caudill, and P. J. Stover, “A UV-responsive internal ribosome entry site enhances serine hydroxymethyltransferase 1 expression for DNA damage repair,” The Journal of Biological Chemistry, vol. 284, no. 45, pp. 31097–31108, 2009.
[55]
M. J. Morris, Y. Negishi, C. Pazsint, J. D. Schonhoft, and S. Basu, “An RNA G-quadruplex is essential for cap-independent translation initiation in human VEGF IRES,” Journal of the American Chemical Society, vol. 132, no. 50, pp. 17831–17839, 2010.
[56]
A. Riley, L. E. Jordan, and M. Holcik, “Distinct 5′ UTRs regulate XIAP expression under normal growth conditions and during cellular stress,” Nucleic Acids Research, vol. 38, no. 14, pp. 4665–4674, 2010.
[57]
T. E. Graber, S. D. Baird, P. N. Kao, M. B. Mathews, and M. Holcik, “NF45 functions as an IRES transacting factor that is required for translation of cIAP1 during the unfolded protein response,” Cell Death and Differentiation, vol. 17, no. 4, pp. 719–729, 2010.
[58]
S. Henis-Korenblit, G. Shani, T. Sines, L. Marash, G. Shohat, and A. Kimchi, “The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 8, pp. 5400–5405, 2002.
[59]
K. A. Spriggs, L. C. Cobbold, S. H. Ridley et al., “The human insulin receptor mRNA contains a functional internal ribosome entry segment,” Nucleic Acids Research, vol. 37, no. 17, pp. 5881–5893, 2009.
[60]
S. A. Mitchell, K. A. Spriggs, M. J. Coldwell, R. J. Jackson, and A. E. Willis, “The Apaf-1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr,” Molecular Cell, vol. 11, no. 3, pp. 757–771, 2003.
[61]
L. Marash, N. Liberman, S. Henis-Korenblit et al., “DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis,” Molecular Cell, vol. 30, no. 4, pp. 447–459, 2008.
[62]
G. Hernández, P. Vázquez-Pianzola, J. M. Sierra, and R. Rivera-Pomar, “Internal ribosome entry site drives cap-independent translation of reaper and heat shock protein 70 mRNAs in Drosophila embryos,” RNA, vol. 10, no. 11, pp. 1783–1797, 2004.
[63]
P. Vazquez-Pianzola, G. Hernández, B. Suter, and R. Rivera-Pomar, “Different modes of translation for hid, grim and sickle mRNAs in Drosophila,” Cell Death and Differentiation, vol. 14, no. 2, pp. 286–295, 2007.
[64]
S. K. Oh, M. P. Scott, and P. Sarnow, “Homeotic gene Antennapedia mRNA contains 5′-noncoding sequences that confer translational initiation by internal ribosome binding,” Genes and Development, vol. 6, no. 9, pp. 1643–1653, 1992.
[65]
B. P. Tsai, X. Wang, L. Huang, and M. L. Waterman, “Quantitative profiling of in vivo-assembled RNA-protein complexes using a novel integrated proteomic approach,” Molecular & Cellular Proteomics, vol. 10, no. 4, article M110 007385, 2011.
[66]
O. Sella, G. Gerlitz, S. Y. Le, and O. Elroy-Stein, “Differentiation-induced internal translation of c-sis mRNA: analysis of the cis elements and their differentiation-linked binding to the hnRNP C protein,” Molecular and Cellular Biology, vol. 19, no. 8, pp. 5429–5440, 1999.
[67]
E. Villa-Cuesta, B. T. Sage, and M. Tatar, “A role for drosophila dFoxO and dFoxO 5′UTR internal ribosomal entry sites during fasting,” PLoS ONE, vol. 5, no. 7, article e11521, 2010.
[68]
M. T. Marr, J. A. D'Alessio, O. Puig, and R. Tjian, “IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback,” Genes and Development, vol. 21, no. 2, pp. 175–183, 2007.
[69]
P. Ramanathan, J. Guo, R. N. Whitehead, and S. Brogna, “The intergenic spacer of the Drosophila Adh-Adhr dicistronic mRNA stimulates internal translation initiation,” RNA Biology, vol. 5, no. 3, pp. 149–156, 2008.
[70]
T. D. Dinkova, H. Zepeda, E. Martinez-Salas, L. M. Martinez, J. Nieto-Sotelo, and S. E. de Jimenez, “Cap-independent translation of maize Hsp101,” Plant Journal, vol. 41, no. 5, pp. 722–731, 2005.
[71]
E. S. Mardanova, L. A. Zamchuk, M. V. Skulachev, and N. V. Ravin, “The 5′ untranslated region of the maize alcohol dehydrogenase gene contains an internal ribosome entry site,” Gene, vol. 420, no. 1, pp. 11–16, 2008.
[72]
L. C. Reineke and W. C. Merrick, “Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression,” RNA, vol. 15, no. 12, pp. 2264–2277, 2009.
[73]
W. V. Gilbert, K. Zhou, T. K. Butler, and J. A. Doudna, “Cap-independent translation is required for starvation-induced differentiation in yeast,” Science, vol. 317, no. 5842, pp. 1224–1227, 2007.
[74]
M. Mokrejs, V. Vopalensky, O. Kolenaty, et al., “IRESite: the database of experimentally verified IRES structures (http://www.iresite.org/),” Nucleic Acids Research, vol. 34, pp. D125–D130, 2006.
[75]
T. Y. Wu, C. C. Hsieh, J. J. Hong, C. Y. Chen, and Y. S. Tsai, “IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,” BMC Bioinformatics, vol. 10, article 160, 2009.
[76]
S. López de Quinto and E. Martínez-Salas, “Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection,” Virology, vol. 255, no. 2, pp. 324–336, 1999.
[77]
J. P. C. Le Quesne, M. Stoneley, G. A. Fraser, and A. E. Willis, “Derivation of a structural model for the c-myc IRES,” Journal of Molecular Biology, vol. 310, no. 1, pp. 111–126, 2001.
[78]
G. Grillo, A. Turi, F. Licciulli et al., “UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs,” Nucleic Acids Research, vol. 38, no. 1, pp. D75–D80, 2009.
[79]
E. Martínez-Salas, A. Pacheco, P. Serrano, and N. Fernandez, “New insights into internal ribosome entry site elements relevant for viral gene expression,” Journal of General Virology, vol. 89, no. 3, pp. 611–626, 2008.
[80]
M. Rodríguez Pulido, P. Serrano, M. Sáiz, and E. Martínez-Salas, “Foot-and-mouth disease virus infection induces proteolytic cleavage of PTB, eIF3a,b, and PABP RNA-binding proteins,” Virology, vol. 364, no. 2, pp. 466–474, 2007.
[81]
E. Martinez-Salas and M. Ryan, “Translation and protein processing,” in Picornaviruses, E. Ehrenfeld, E. Domingo, and R. Roos, Eds., pp. 141–161, ASM Press, 2010.
[82]
D. E. Andreev, O. Fernandez-Miragall, J. Ramajo et al., “Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNA,” RNA, vol. 13, no. 8, pp. 1366–1374, 2007.
[83]
S. de Breyne, Y. Yu, A. Unbehaun, T. V. Pestova, and C. U. T. Hellen, “Direct functional interaction of initiation factor eIF4G with type 1 internal ribosomal entry sites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 23, pp. 9197–9202, 2009.
[84]
S. López de Quinto, E. Lafuente, and E. Martínez-Salas, “IRES interaction with translation initiation factors: functional characterization of novel RNA contacts with eIF3, eIF4B, and eIF4GII,” RNA, vol. 7, no. 9, pp. 1213–1226, 2001.
[85]
O. Fernandez-Miragall, S. Lopez de Quinto, and E. Martinez-Salas, “Relevance of RNA structure for the activity of picornavirus IRES elements,” Virus Research, vol. 139, pp. 172–182, 2009.
[86]
K. E. Berry, S. Waghray, S. A. Mortimer, Y. Bai, and J. A. Doudna, “Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning,” Structure, vol. 19, pp. 1456–1466, 2011.
[87]
N. Locker, L. E. Easton, and P. J. Lukavsky, “HCV and CSFV IRES domain II mediate eIF2 release during 80S ribosome assembly,” The EMBO Journal, vol. 26, no. 3, pp. 795–805, 2007.
[88]
C. M. T. Spahn, J. S. Kieft, R. A. Grassucci et al., “Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit,” Science, vol. 291, no. 5510, pp. 1959–1962, 2001.
[89]
S. de Breyne, Y. Yu, T. V. Pestova, and C. U. T. Hellen, “Factor requirements for translation initiation on the Simian picornavirus internal ribosomal entry site,” RNA, vol. 14, no. 2, pp. 367–380, 2008.
[90]
L. E. Easton, N. Locker, and P. J. Lukavsky, “Conserved functional domains and a novel tertiary interaction near the pseudoknot drive translational activity of hepatitis C virus and hepatitis C virus-like internal ribosome entry sites,” Nucleic Acids Research, vol. 37, no. 16, pp. 5537–5549, 2009.
[91]
D. A. Costantino, J. S. Pfingsten, R. P. Rambo, and J. S. Kieft, “tRNA-mRNA mimicry drives translation initiation from a viral IRES,” Nature Structural and Molecular Biology, vol. 15, no. 1, pp. 57–64, 2008.
[92]
J. Sasaki and N. Nakashima, “Translation initiation at the CUU codon is mediated by the internal ribosome entry site of an insect picorna-like virus in vitro,” Journal of Virology, vol. 73, no. 2, pp. 1219–1226, 1999.
[93]
N. Nakashima and T. Uchiumi, “Functional analysis of structural motifs in dicistroviruses,” Virus Research, vol. 139, no. 2, pp. 137–147, 2009.
[94]
G. Johannes, M. S. Carter, M. B. Eisen, P. O. Brown, and P. Sarnow, “Identification of eukaryotic mRNAs that are translated at reduced cap binding complex elF4F concentrations using a cDNA microarray,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 23, pp. 13118–13123, 1999.
[95]
C. M. T. Spahn, E. Jan, A. Mulder, R. A. Grassucci, P. Sarnow, and J. Frank, “Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: the IRES functions as an RNA-based translation factor,” Cell, vol. 118, no. 4, pp. 465–475, 2004.
[96]
T. V. Pestova, I. N. Shatsky, S. P. Fletcher, R. J. Jackson, and C. U. T. Hellen, “A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initation of hepatitis C and classical swine fever virus RNAs,” Genes and Development, vol. 12, no. 1, pp. 67–83, 1998.
[97]
S. Lopez de Quinto and E. Martinez-Salas, “Interaction of the elF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo,” RNA, vol. 6, no. 10, pp. 1380–1392, 2000.
[98]
E. Martinez-Salas, M. P. Regalado, and E. Domingo, “Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution,” Journal of Virology, vol. 70, no. 2, pp. 992–998, 1996.
[99]
E. Martinez-Salas and O. Fernandez-Miragall, “Picornavirus IRES: structure function relationship,” Current Pharmaceutical Design, vol. 10, pp. 3757–3767, 2004.
[100]
M. Honda, R. Rijnbrand, G. Abell, D. Kim, and S. M. Lemon, “Natural variation in translational activities of the 5′ nontranslated RNAs of hepatitis C virus genotypes 1a and 1b: evidence for a long-range RNA- RNA interaction outside of the internal ribosomal entry site,” Journal of Virology, vol. 73, no. 6, pp. 4941–4951, 1999.
[101]
J. C. Saiz, S. Lopez de Quinto, N. Ibarrola, et al., “Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients,” Archives of Virology, vol. 144, pp. 215–229, 1999.
[102]
M. I. Barria, A. Gonzalez, J. Vera-Otarola, et al., “Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation,” Nucleic Acids Research, vol. 37, pp. 957–971, 2009.
[103]
P. Serrano, J. Ramajo, and E. Martínez-Salas, “Rescue of internal initiation of translation by RNA complementation provides evidence for a distribution of functions between individual IRES domains,” Virology, vol. 388, no. 1, pp. 221–229, 2009.
[104]
C. J. Jang and E. Jan, “Modular domains of the Dicistroviridae intergenic internal ribosome entry site,” RNA, vol. 16, no. 6, pp. 1182–1195, 2010.
[105]
C. L. Jopling, K. A. Spriggs, S. A. Mitchell, M. Stoneley, and A. E. Willis, “L-Myc protein synthesis is initiated by internal ribosome entry,” RNA, vol. 10, no. 2, pp. 287–298, 2004.
[106]
N. Fernandez, O. Fernandez-Miragall, J. Ramajo, et al., “Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translation,” Nucleic Acids Research, vol. 39, pp. 8572–8585, 2011.
[107]
Y. Yu, I. S. Abaeva, A. Marintchev, T. V. Pestova, and C. U. Hellen, “Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors,” Nucleic Acids Research, vol. 39, pp. 4851–4865, 2011.
[108]
N. Fernandez, A. Garcia-Sacristan, J. Ramajo, C. Briones, and E. Martinez-Salas, “Structural analysis provides insights into the modular organization of picornavirus IRES,” Virology, vol. 409, pp. 251–261, 2011.
[109]
R. Ramos and E. Martínez-Salas, “Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES),” RNA, vol. 5, no. 10, pp. 1374–1383, 1999.
[110]
O. Fernandez-Miragall, R. Ramos, J. Ramajo, and E. Martinez-Salas, “Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation,” RNA, vol. 12, pp. 223–234, 2006.
[111]
O. Fernandez-Miragall and E. Martinez-Salas, “Structural organization of a viral IRES depends on the integrity of the GNRA motif,” RNA, vol. 9, pp. 1333–1344, 2003.
[112]
M. Phelan, R. J. Banks, G. Conn, and V. Ramesh, “NMR studies of the structure and Mg2+ binding properties of a conserved RNA motif of EMCV picornavirus IRES element,” Nucleic Acids Research, vol. 32, no. 16, pp. 4715–4724, 2004.
[113]
Z. Du, N. B. Ulyanov, J. Yu, R. Andino, and T. L. James, “NMR structures of loop B RNAs from the stem-loop IV domain of the enterovirus internal ribosome entry site: a single C to U substitution drastically changes the shape and flexibility of RNA,” Biochemistry, vol. 43, no. 19, pp. 5757–5771, 2004.
[114]
S. Lopez de Quinto and E. Martinez-Salas, “Conserved structural motifs located in distal loops of aphthovirus internal ribosome entry site domain 3 are required for internal initiation of translation,” Journal of Virology, vol. 71, pp. 4171–4175, 1997.
[115]
M. E. M. Robertson, R. A. Seamons, and G. J. Belsham, “A selection system for functional internal ribosome entry site (IRES) elements: analysis of the requirement for a conserved GNRA tetraloop in the encephalomyocarditis virus IRES,” RNA, vol. 5, no. 9, pp. 1167–1179, 1999.
[116]
D. M. Landry, M. I. Hertz, and S. R. Thompson, “RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs,” Genes and Development, vol. 23, no. 23, pp. 2753–2764, 2009.
[117]
A. Nadal, M. Martell, J. R. Lytle et al., “Specific cleavage of hepatitis C virus RNA genome by human RNase P,” The Journal of Biological Chemistry, vol. 277, no. 34, pp. 30606–30613, 2002.
[118]
A. J. Lyons and H. D. Robertson, “Detection of tRNA-like structure through RNase P cleavage of viral internal ribosome entry site RNAs near the AUG start triplet,” The Journal of Biological Chemistry, vol. 278, no. 29, pp. 26844–26850, 2003.
[119]
P. Serrano, J. Gomez, and E. Martínez-Salas, “Characterization of a cyanobacterial RNase P ribozyme recognition motif in the IRES of foot-and-mouth disease virus reveals a unique structural element,” RNA, vol. 13, no. 6, pp. 849–859, 2007.
[120]
N. Fernandez and E. Martinez-Salas, “Tailoring the switch from IRES-dependent to 5′-end-dependent translation with the RNase P ribozyme,” RNA, vol. 16, pp. 852–862.
[121]
M. Piron, N. Beguiristain, A. Nadal, E. Martinez-Salas, and J. Gomez, “Characterizing the function and structural organization of the 5′ tRNA-like motif within the hepatitis C virus quasispecies,” Nucleic Acids Research, vol. 33, pp. 1487–1502, 2005.
[122]
G. Hernández, “Was the initiation of translation in early eukaryotes IRES-driven?” Trends in Biochemical Sciences, vol. 33, no. 2, pp. 58–64, 2008.
[123]
F. Martínez-Azorín, M. Remacha, E. Martínez-Salas, and J. P. G. Ballesta, “Internal translation initiation on the foot-and-mouth disease virus IRES is affected by ribosomal stalk conformation,” FEBS Letters, vol. 582, no. 20, pp. 3029–3032, 2008.
[124]
C. Yang, C. Zhang, J. D. Dittman, and S. A. Whitham, “Differential requirement of ribosomal protein S6 by plant RNA viruses with different translation initiation strategies,” Virology, vol. 390, no. 2, pp. 163–173, 2009.
[125]
A. Basu, P. Das, S. Chaudhuri, et al., “Requirement of rRNA methylation for 80S ribosome assembly on a cohort of cellular Internal Ribosome Entry Sites,” Molecular and Cellular Biology, vol. 31, pp. 4482–4499, 2011.
[126]
R. Horos, H. Ijspeert, D. Pospisilova, et al., “Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts,” Blood, vol. 119, pp. 262–272, 2012.
[127]
X. Yuan, K. Shi, M. Y. L. Young, and A. E. Simon, “The terminal loop of a 3′ proximal hairpin plays a critical role in replication and the structure of the 3′ region of Turnip crinkle virus,” Virology, vol. 402, no. 2, pp. 271–280, 2010.
[128]
P. Serrano, M. R. Pulido, M. Saiz, and E. Martinez-Salas, “The 3′ end of the foot-and-mouth disease virus genome establishes two distinct long-range RNA-RNA interactions with the 5′ end region,” Journal of General Virology, vol. 87, pp. 3013–3022, 2006.
[129]
C. Romero-López and A. Berzal-Herranz, “A long-range RNA-RNA interaction between the 5′ and 3′ ends of the HCV genome,” RNA, vol. 15, no. 9, pp. 1740–1752, 2009.
[130]
S. Lopez de Quinto, M. Saiz, D. de la Morena, F. Sobrino, and E. Martinez-Salas, “IRES-driven translation is stimulated separately by the FMDV 3′-NCR and poly(A) sequences,” Nucleic Acids Research, vol. 30, pp. 4398–4405, 2002.
[131]
E. Dobrikova, P. Florez, S. Bradrick, and M. Gromeier, “Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15125–15130, 2003.
[132]
M. Saiz, S. Gomez, E. Martinez-Salas, and F. Sobrino, “Deletion or substitution of the aphthovirus 3′ NCR abrogates infectivity and virus replication,” Journal of General Virology, vol. 82, pp. 93–101, 2001.
[133]
S. Weinlich, S. Hüttelmaier, A. Schierhorn, S. E. Behrens, A. Ostareck-Lederer, and D. H. Ostareck, “IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3′UTR,” RNA, vol. 15, no. 8, pp. 1528–1542, 2009.
[134]
A. Pacheco and E. Martinez-Salas, “Insights into the biology of IRES elements through riboproteomic approaches,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 458927, 12 pages, 2010.
[135]
A. Pacheco, S. Reigadas, and E. Martínez-Salas, “Riboproteomic analysis of polypeptides interacting with the internal ribosome-entry site element of foot-and-mouth disease viral RNA,” Proteomics, vol. 8, no. 22, pp. 4782–4790, 2008.
[136]
P. Vazquez-Pianzola, H. Urlaub, and R. Rivera-Pomar, “Proteomic analysis of reaper 5′ untranslated region-interacting factors isolated by tobramycin affinity-selection reveals a role for La antigen in reaper mRNA translation,” Proteomics, vol. 5, no. 6, pp. 1645–1655, 2005.
[137]
S. K. Jang and E. Wimmer, “Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein,” Genes and Development, vol. 4, no. 9, pp. 1560–1572, 1990.
[138]
K. M. Bedard, S. Daijogo, and B. L. Semler, “A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation,” The EMBO Journal, vol. 26, no. 2, pp. 459–467, 2007.
[139]
J. Y. Lin, M. L. Li, and S. R. Shih, “Far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation,” Nucleic Acids Research, vol. 37, no. 1, pp. 47–59, 2009.
[140]
A. Pacheco, S. Lopez de Quinto, J. Ramajo, N. Fernandez, and E. Martinez-Salas, “A novel role for Gemin5 in mRNA translation,” Nucleic Acids Research, vol. 37, pp. 582–590, 2009.
[141]
Y. Yu, H. Ji, J. A. Doudna, and J. A. Leary, “Mass spectrometric analysis of the human 40S ribosomal subunit: native and HCV IRES-bound complexes,” Protein Science, vol. 14, no. 6, pp. 1438–1446, 2005.
[142]
S. S. Bradrick and M. Gromeier, “Identification of gemin5 as a novel 7-methylguanosine cap-binding protein,” PLoS ONE, vol. 4, no. 9, article e7030, 2009.
[143]
J. Liu, J. Henao-Mejia, H. Liu, Y. Zhao, and J. J. He, “Translational regulation of HIV-1 replication by HIV-1 Rev cellular cofactors Sam68, eIF5A, hRIP, and DDX3,” Journal of NeuroImmune Pharmacology, vol. 6, pp. 308–321, 2011.
[144]
P. Pan and F. van Breukelen, “Preference of IRES-mediated initiation of translation during hibernation in golden-mantled ground squirrels, Spermophilus lateralis,” American Journal of Physiology, vol. 301, pp. R370–R377, 2011.
[145]
M. Bushell, M. Stoneley, Y. W. Kong et al., “Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis,” Molecular Cell, vol. 23, no. 3, pp. 401–412, 2006.
[146]
X. Xia and M. Holcik, “Strong eukaryotic IRESs have weak secondary structure,” PLoS ONE, vol. 4, no. 1, article e4136, 2009.
[147]
H. C. Dobbyn, K. Hill, T. L. Hamilton et al., “Regulation of BAG-1 IRES-mediated translation following chemotoxic stress,” Oncogene, vol. 27, no. 8, pp. 1167–1174, 2008.
[148]
B. Schepens, S. A. Tinton, Y. Bruynooghe et al., “A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis,” The EMBO Journal, vol. 26, no. 1, pp. 158–169, 2007.
[149]
K. H. Lee, K. C. Woo, D. Y. Kim, et al., “Rhythmic interaction between period1 mRNA and hnRNP Q leads to circadian time-dependent translation,” Molecular and Cellular Biology, vol. 32, pp. 717–728, 2012.
[150]
N. H. Ungureanu, M. Cloutier, S. M. Lewis et al., “Internal ribosome entry site-mediated translation of Apaf-1, but not XIAP, is regulated during UV-induced cell death,” The Journal of Biological Chemistry, vol. 281, no. 22, pp. 15155–15163, 2006.
[151]
A. Cammas, F. Pileur, S. Bonnal et al., “Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein A1 controls translation initiation of specific mRNAs,” Molecular Biology of the Cell, vol. 18, no. 12, pp. 5048–5059, 2007.
[152]
S. M. Lewis, S. Cerquozzi, T. E. Graber, N. H. Ungureanu, M. Andrews, and M. Holcik, “The eIF4G homolog DAP5/p97 supports the translation of select mRNAs during endoplasmic reticulum stress,” Nucleic Acids Research, vol. 36, no. 1, pp. 168–178, 2008.
[153]
M. A. Sammons, A. K. Antons, M. Bendjennat, B. Udd, R. Krahe, and A. J. Link, “ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2,” PLoS ONE, vol. 5, no. 2, article e9301, 2010.
[154]
C. Bellodi, N. Kopmar, and D. Ruggero, “Deregulation of oncogene-induced senescence and p53 translational control in X-linked dyskeratosis congenita,” The EMBO Journal, vol. 29, no. 11, pp. 1865–1876, 2010.
