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Regulation of Translation Initiation under Biotic and Abiotic Stresses  [PDF]
Sira Echevarría-Zome?o,Emilio Yángüez,Nuria Fernández-Bautista,Ana B. Castro-Sanz,Alejandro Ferrando,M. Mar Castellano
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms14034670
Abstract: Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.
Protein synthesis in eukaryotes: The growing biological relevance of cap-independent translation initiation
LóPEZ-LASTRA,MARCELO; RIVAS,ANDREA; BARRíA,MARíA INéS;
Biological Research , 2005, DOI: 10.4067/S0716-97602005000200003
Abstract: ribosome recruitment to eukaryotic mrnas is generally thought to occur by a scanning mechanism, whereby the 40s ribosomal subunit binds in the vicinity of the 5'cap structure of the mrna and scans until an aug codon is encountered in an appropriate sequence context. study of the picornaviruses allowed the characterization of an alternative mechanism of translation initiation. picornaviruses can initiate translation via an internal ribosome entry segment (ires), an rna structure that directly recruits the 40s ribosomal subunits in a cap and 5' end independent fashion. since its discovery, the notion of iress has extended to a number of different virus families and cellular rnas. this review summarizes features of both cap-dependent and ires-dependent mechanisms of translation initiation and discusses the role of cis-acting elements, which include the 5'cap, the 5'-untranslated region (utr) and the poly(a) tail as well as the possible roles of iress as part of a cellular stress response mechanism and in the virus replication cycle
Protein synthesis in eukaryotes: The growing biological relevance of cap-independent translation initiation
MARCELO LóPEZ-LASTRA,ANDREA RIVAS,MARíA INéS BARRíA
Biological Research , 2005,
Abstract: Ribosome recruitment to eukaryotic mRNAs is generally thought to occur by a scanning mechanism, whereby the 40S ribosomal subunit binds in the vicinity of the 5'cap structure of the mRNA and scans until an AUG codon is encountered in an appropriate sequence context. Study of the picornaviruses allowed the characterization of an alternative mechanism of translation initiation. Picornaviruses can initiate translation via an internal ribosome entry segment (IRES), an RNA structure that directly recruits the 40S ribosomal subunits in a cap and 5' end independent fashion. Since its discovery, the notion of IRESs has extended to a number of different virus families and cellular RNAs. This review summarizes features of both cap-dependent and IRES-dependent mechanisms of translation initiation and discusses the role of cis-acting elements, which include the 5'cap, the 5'-untranslated region (UTR) and the poly(A) tail as well as the possible roles of IRESs as part of a cellular stress response mechanism and in the virus replication cycle
A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes  [PDF]
Wanjun Gu ,Tong Zhou ,Claus O. Wilke
PLOS Computational Biology , 2010, DOI: 10.1371/journal.pcbi.1000664
Abstract: Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.
Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance
Liuqiang Wang, Chenxi Xu, Chao Wang, Yucheng Wang
BMC Plant Biology , 2012, DOI: 10.1186/1471-2229-12-118
Abstract: In this study, we characterized the function of eIF5A (TaeIF5A1) from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486?bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY) and RAV (TaRAV) protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA) signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activities, lower electrolyte leakage and higher chlorophyll content under salt stress.These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.Eukaryotic initiation factor 5A (eIF5A) is a small protein ubiquitously present throughout the eukaryotic kingdom. The protein was initially identified in rabbit reticulocytes as a factor involved in formation of the first peptide bond [1,2]. EIF5A is a highly conserved protein and contains the post-translationally synthesized amino acid hypusine [3]. Molecular and biochemical studies in yeast and mammalian cells demonstrated that eIF5A is synthesized as an inactive precursor that is activated by a post-translational hypusine modification that is only detected in the eIF5A protein,
Leaderless genes in bacteria: clue to the evolution of translation initiation mechanisms in prokaryotes
Xiaobin Zheng, Gang-Qing Hu, Zhen-Su She, Huaiqiu Zhu
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-361
Abstract: Here, we study signals in translation initiation regions of all genes over 953 bacterial and 72 archaeal genomes, then make an effort to construct an evolutionary scenario in view of leaderless genes in bacteria. With an algorithm designed to identify multi-signal in upstream regions of genes for a genome, we classify all genes into SD-led, TA-led and atypical genes according to the category of the most probable signal in their upstream sequences. Particularly, occurrence of TA-like signals about 10 bp upstream to translation initiation site (TIS) in bacteria most probably means leaderless genes.Our analysis reveals that leaderless genes are totally widespread, although not dominant, in a variety of bacteria. Especially for Actinobacteria and Deinococcus-Thermus, more than twenty percent of genes are leaderless. Analyzed in closely related bacterial genomes, our results imply that the change of translation initiation mechanisms, which happens between the genes deriving from a common ancestor, is linearly dependent on the phylogenetic relationship. Analysis on the macroevolution of leaderless genes further shows that the proportion of leaderless genes in bacteria has a decreasing trend in evolution.As the first stage of protein synthesis in gene expression, translation is a key process highly conserved in the biological system. Up to now, 31 universally occurring genes identified in 191 species are shown being involved in the translation process [1]. However, translation initiation shows great variation in the three kingdoms. In eukaryotes, the ribosome binds at the 5'-end of the capped mRNA and slides downstream to find the first start codon and then initiate the translation, which is the so-called scanning mechanism [2]. In prokaryotes, there are two known mechanisms. The Shine-Dalgarno (SD) initiation mechanism was found early in Escherichia coli [3]. For this mechanism, a short motif called SD sequence in the 5'-untranslated region (5'-UTR) on mRNA binds with the
A Conserved Interaction between a C-Terminal Motif in Norovirus VPg and the HEAT-1 Domain of eIF4G Is Essential for Translation Initiation  [PDF]
Eoin N. Leen?,Frédéric Sorgeloos?,Samantha Correia?,Yasmin Chaudhry?,Fabien Cannac?,Chiara Pastore?,Yingqi Xu?,Stephen C. Graham?,Stephen J. Matthews?,Ian G. Goodfellow
PLOS Pathogens , 2016, DOI: 10.1371/journal.ppat.1005379
Abstract: Translation initiation is a critical early step in the replication cycle of the positive-sense, single-stranded RNA genome of noroviruses, a major cause of gastroenteritis in humans. Norovirus RNA, which has neither a 5′ m7G cap nor an internal ribosome entry site (IRES), adopts an unusual mechanism to initiate protein synthesis that relies on interactions between the VPg protein covalently attached to the 5′-end of the viral RNA and eukaryotic initiation factors (eIFs) in the host cell. For murine norovirus (MNV) we previously showed that VPg binds to the middle fragment of eIF4G (4GM; residues 652–1132). Here we have used pull-down assays, fluorescence anisotropy, and isothermal titration calorimetry (ITC) to demonstrate that a stretch of ~20 amino acids at the C terminus of MNV VPg mediates direct and specific binding to the HEAT-1 domain within the 4GM fragment of eIF4G. Our analysis further reveals that the MNV C terminus binds to eIF4G HEAT-1 via a motif that is conserved in all known noroviruses. Fine mutagenic mapping suggests that the MNV VPg C terminus may interact with eIF4G in a helical conformation. NMR spectroscopy was used to define the VPg binding site on eIF4G HEAT-1, which was confirmed by mutagenesis and binding assays. We have found that this site is non-overlapping with the binding site for eIF4A on eIF4G HEAT-1 by demonstrating that norovirus VPg can form ternary VPg-eIF4G-eIF4A complexes. The functional significance of the VPg-eIF4G interaction was shown by the ability of fusion proteins containing the C-terminal peptide of MNV VPg to inhibit in vitro translation of norovirus RNA but not cap- or IRES-dependent translation. These observations define important structural details of a functional interaction between norovirus VPg and eIF4G and reveal a binding interface that might be exploited as a target for antiviral therapy.
Conservation of the RNA Transport Machineries and Their Coupling to Translation Control across Eukaryotes  [PDF]
Paula Vazquez-Pianzola,Beat Suter
Comparative and Functional Genomics , 2012, DOI: 10.1155/2012/287852
Abstract: Restriction of proteins to discrete subcellular regions is a common mechanism to establish cellular asymmetries and depends on a coordinated program of mRNA localization and translation control. Many processes from the budding of a yeast to the establishment of metazoan embryonic axes and the migration of human neurons, depend on this type of cell polarization. How factors controlling transport and translation assemble to regulate at the same time the movement and translation of transported mRNAs, and whether these mechanisms are conserved across kingdoms is not yet entirely understood. In this review we will focus on some of the best characterized examples of mRNA transport machineries, the “yeast locasome” as an example of RNA transport and translation control in unicellular eukaryotes, and on the Drosophila Bic-D/Egl/Dyn RNA localization machinery as an example of RNA transport in higher eukaryotes. This focus is motivated by the relatively advanced knowledge about the proteins that connect the localizing mRNAs to the transport motors and the many well studied proteins involved in translational control of specific transcripts that are moved by these machineries. We will also discuss whether the core of these RNA transport machineries and factors regulating mRNA localization and translation are conserved across eukaryotes.
On the Diversification of the Translation Apparatus across Eukaryotes  [PDF]
Greco Hernández,Christopher G. Proud,Thomas Preiss,Armen Parsyan
Comparative and Functional Genomics , 2012, DOI: 10.1155/2012/256848
Abstract: Diversity is one of the most remarkable features of living organisms. Current assessments of eukaryote biodiversity reaches 1.5 million species, but the true figure could be several times that number. Diversity is ingrained in all stages and echelons of life, namely, the occupancy of ecological niches, behavioral patterns, body plans and organismal complexity, as well as metabolic needs and genetics. In this review, we will discuss that diversity also exists in a key biochemical process, translation, across eukaryotes. Translation is a fundamental process for all forms of life, and the basic components and mechanisms of translation in eukaryotes have been largely established upon the study of traditional, so-called model organisms. By using modern genome-wide, high-throughput technologies, recent studies of many nonmodel eukaryotes have unveiled a surprising diversity in the configuration of the translation apparatus across eukaryotes, showing that this apparatus is far from being evolutionarily static. For some of the components of this machinery, functional differences between different species have also been found. The recent research reviewed in this article highlights the molecular and functional diversification the translational machinery has undergone during eukaryotic evolution. A better understanding of all aspects of organismal diversity is key to a more profound knowledge of life.
On the Diversification of the Translation Apparatus across Eukaryotes  [PDF]
Greco Hernández,Christopher G. Proud,Thomas Preiss,Armen Parsyan
International Journal of Genomics , 2012, DOI: 10.1155/2012/256848
Abstract: Diversity is one of the most remarkable features of living organisms. Current assessments of eukaryote biodiversity reaches 1.5 million species, but the true figure could be several times that number. Diversity is ingrained in all stages and echelons of life, namely, the occupancy of ecological niches, behavioral patterns, body plans and organismal complexity, as well as metabolic needs and genetics. In this review, we will discuss that diversity also exists in a key biochemical process, translation, across eukaryotes. Translation is a fundamental process for all forms of life, and the basic components and mechanisms of translation in eukaryotes have been largely established upon the study of traditional, so-called model organisms. By using modern genome-wide, high-throughput technologies, recent studies of many nonmodel eukaryotes have unveiled a surprising diversity in the configuration of the translation apparatus across eukaryotes, showing that this apparatus is far from being evolutionarily static. For some of the components of this machinery, functional differences between different species have also been found. The recent research reviewed in this article highlights the molecular and functional diversification the translational machinery has undergone during eukaryotic evolution. A better understanding of all aspects of organismal diversity is key to a more profound knowledge of life. 1. Protein Synthesis Is a Fundamental Process of Life Proteins are one of the elementary components of life and account for a large fraction of mass in the biosphere. They catalyze most reactions that sustain life and play structural, transport, and regulatory roles in all living organisms. Hence, “translation,” that is, the synthesis of proteins by the ribosome using messenger (m)RNA as the template, is a fundamental process for all forms of life, and a large proportion of an organism’s energy is committed to translation [1, 2]. Accordingly, regulating protein synthesis is crucial for all organisms. Indeed, many mechanisms to control gene expression at the translational level have evolved in eukaryotes [3]. These mechanisms have endowed eukaryotes with the potential to rapidly and reversibly respond to stress or sudden environmental changes [1, 2, 4]. Translational control also plays a crucial role in tissues and developmental processes where transcription is quiescent, or where asymmetric spatial localization of proteins is required, such as early embryogenesis, learning and memory, neurogenesis, and gametogenesis [5–10]. Moreover, recent global gene expression
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