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Comparative genomics of eukaryotic small nucleolar RNAs reveals deep evolutionary ancestry amidst ongoing intragenomic mobility  [cached]
Hoeppner Marc P,Poole Anthony M
BMC Evolutionary Biology , 2012, DOI: 10.1186/1471-2148-12-183
Abstract: Background Small nucleolar (sno)RNAs are required for posttranscriptional processing and modification of ribosomal, spliceosomal and messenger RNAs. Their presence in both eukaryotes and archaea indicates that snoRNAs are evolutionarily ancient. The location of some snoRNAs within the introns of ribosomal protein genes has been suggested to belie an RNA world origin, with the exons of the earliest protein-coding genes having evolved around snoRNAs after the advent of templated protein synthesis. Alternatively, this intronic location may reflect more recent selection for coexpression of snoRNAs and ribosomal components, ensuring rRNA modification by snoRNAs during ribosome synthesis. To gain insight into the evolutionary origins of this genetic organization, we examined the antiquity of snoRNA families and the stability of their genomic location across 44 eukaryote genomes. Results We report that dozens of snoRNA families are traceable to the Last Eukaryotic Common Ancestor (LECA), but find only weak similarities between the oldest eukaryotic snoRNAs and archaeal snoRNA-like genes. Moreover, many of these LECA snoRNAs are located within the introns of host genes independently traceable to the LECA. Comparative genomic analyses reveal the intronic location of LECA snoRNAs is not ancestral however, suggesting the pattern we observe is the result of ongoing intragenomic mobility. Analysis of human transcriptome data indicates that the primary requirement for hosting intronic snoRNAs is a broad expression profile. Consistent with ongoing mobility across broadly-expressed genes, we report a case of recent migration of a non-LECA snoRNA from the intron of a ubiquitously expressed non-LECA host gene into the introns of two LECA genes during the evolution of primates. Conclusions Our analyses show that snoRNAs were a well-established family of RNAs at the time when eukaryotes began to diversify. While many are intronic, this association is not evolutionarily stable across the eukaryote tree; ongoing intragenomic mobility has erased signal of their ancestral gene organization, and neither introns-first nor evolved co-expression adequately explain our results. We therefore present a third model — constrained drift — whereby individual snoRNAs are intragenomically mobile and may occupy any genomic location from which expression satisfies phenotype.
Full-length cDNA sequences from Rhesus monkey placenta tissue: analysis and utility for comparative mapping
Dae-Soo Kim, Jae-Won Huh, Young-Hyun Kim, Sang-Je Park, Sang-Rae Lee, Kyu-Tae Chang
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-427
Abstract: From rhesus monkey placenta full-length cDNA libraries, 2000 full-length cDNA sequences were determined and 1835 rhesus placenta cDNA sequences longer than 100 bp were collected. These sequences were annotated based on homology to human genes. Homology search against human RefSeq mRNAs revealed that our collection included the sequences of 1462 putative rhesus monkey genes. Moreover, we identified 207 genes containing exon alterations in the coding region and the untranslated region of rhesus monkey transcripts, despite the highly conserved structure of the coding regions. Approximately 10% (187) of all full-length cDNA sequences did not represent any public human RefSeq mRNAs. Intriguingly, two rhesus monkey specific exons derived from the transposable elements of AluYRa2 (SINE family) and MER11B (LTR family) were also identified.The 1835 rhesus monkey placenta full-length cDNA sequences described here could expand genomic resources and information of rhesus monkeys. This increased genomic information will greatly contribute to the development of evolutionary biology and biomedical research.The rhesus monkey (Macaca mulatta) is one of the species of Macaca, an Old World monkey. On the basis of DNA sequence comparison complemented by fossil evidence, the divergence of humans and Old World monkeys is estimated at about 25 million years ago [1]. The relationship between humans and rhesus monkeys is even more important because biomedical research has come to depend on these primates as experimental animal models [2]. Due to their genetic, physiologic, and metabolic similarity to humans, this species serves as an essential research tool in neuroscience, behavioral biology, reproductive physiology, neuroendocrinology, endocrinology, cardiovascular studies, pharmacology and many other areas [3-5].The draft sequence of the rhesus monkey genome, which has an important evolutionary position, was published in 2007 [2]. The final challenge comes in the understanding of basic r
Unusual Vesical Calculus in Rhesus Monkey (Macaca mulatta)
Hong Wang,Wei Si,Yuyu Niu,Lixian Chen,Ye Yan
Journal of Animal and Veterinary Advances , 2012, DOI: 10.3923/javaa.2012.1790.1792
Abstract: Several cases of urinary calculi have been reported in cynomolgus monkeys but vesical calculi were not reported in rhesus monkeys. The adult male rhesus monkey (Macaca mulatta) presented here had a vesical calculi which was entire urate.
Newly Identified CYP2C93 Is a Functional Enzyme in Rhesus Monkey, but Not in Cynomolgus Monkey  [PDF]
Yasuhiro Uno,Shotaro Uehara,Sakae Kohara,Kazuhide Iwasaki,Ryoichi Nagata,Koichiro Fukuzaki,Masahiro Utoh,Norie Murayama,Hiroshi Yamazaki
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016923
Abstract: Cynomolgus monkey and rhesus monkey are used in drug metabolism studies due to their evolutionary closeness and physiological resemblance to human. In cynomolgus monkey, we previously identified cytochrome P450 (P450 or CYP) 2C76 that does not have a human ortholog and is partly responsible for species differences in drug metabolism between cynomolgus monkey and human. In this study, we report characterization of CYP2C93 cDNA newly identified in cynomolgus monkey and rhesus monkey. The CYP2C93 cDNA contained an open reading frame of 490 amino acids approximately 84–86% identical to human CYP2Cs. CYP2C93 was located in the genomic region, which corresponded to the intergenic region in the human genome, indicating that CYP2C93 does not correspond to any human genes. CYP2C93 mRNA was expressed predominantly in the liver among 10 tissues analyzed. The CYP2C93 proteins heterologously expressed in Escherichia coli metabolized human CYP2C substrates, diclofenac, flurbiprofen, paclitaxel, S-mephenytoin, and tolbutamide. In addition to a normal transcript (SV1), an aberrantly spliced transcript (SV2) lacking exon 2 was identified, which did not give rise to a functional protein due to frameshift and a premature termination codon. Mini gene assay revealed that the genetic variant IVS2-1G>T at the splice site of intron 1, at least partly, accounted for the exon-2 skipping; therefore, this genotype would influence CYP2C93-mediated drug metabolism. SV1 was expressed in 6 of 11 rhesus monkeys and 1 of 8 cynomolgus monkeys, but the SV1 in the cynomolgus monkey was nonfunctional due to a rare null genotype (c.102T>del). These results suggest that CYP2C93 can play roles as a drug-metabolizing enzyme in rhesus monkeys (not in cynomolgus monkeys), although its relative contribution to drug metabolism has yet to be validated.
Mammalian Small Nucleolar RNAs Are Mobile Genetic Elements  [PDF]
Michel J Weber
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020205
Abstract: Small nucleolar RNAs (snoRNAs) of the H/ACA box and C/D box categories guide the pseudouridylation and the 2′-O-ribose methylation of ribosomal RNAs by forming short duplexes with their target. Similarly, small Cajal body–specific RNAs (scaRNAs) guide modifications of spliceosomal RNAs. The vast majority of vertebrate sno/scaRNAs are located in introns of genes transcribed by RNA polymerase II and processed by exonucleolytic trimming after splicing. A bioinformatic search for orthologues of human sno/scaRNAs in sequenced mammalian genomes reveals the presence of species- or lineage-specific sno/scaRNA retroposons (sno/scaRTs) characterized by an A-rich tail and an ~14-bp target site duplication that corresponds to their insertion site, as determined by interspecific genomic alignments. Three classes of snoRTs are defined based on the extent of intron and exon sequences from the snoRNA parental host gene they contain. SnoRTs frequently insert in gene introns in the sense orientation at genomic hot spots shared with other genetic mobile elements. Previously characterized human snoRNAs are encoded in retroposons whose parental copies can be identified by phylogenic analysis, showing that snoRTs can be faithfully processed. These results identify snoRNAs as a new family of mobile genetic elements. The insertion of new snoRNA copies might constitute a safeguard mechanism by which the biological activity of snoRNAs is maintained in spite of the risk of mutations in the parental copy. I furthermore propose that retroposition followed by genetic drift is a mechanism that increased snoRNA diversity during vertebrate evolution to eventually acquire new RNA-modification functions.
Expression and Processing of a Small Nucleolar RNA from the Epstein-Barr Virus Genome  [PDF]
Roland Hutzinger equal contributor,Regina Feederle equal contributor,Jan Mrazek,Natalia Schiefermeier,Piotr J. Balwierz,Mihaela Zavolan,Norbert Polacek,Henri-Jacques Delecluse ,Alexander Hüttenhofer
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000547
Abstract: Small nucleolar RNAs (snoRNAs) are localized within the nucleolus, a sub-nuclear compartment, in which they guide ribosomal or spliceosomal RNA modifications, respectively. Up until now, snoRNAs have only been identified in eukaryal and archaeal genomes, but are notably absent in bacteria. By screening B lymphocytes for expression of non-coding RNAs (ncRNAs) induced by the Epstein-Barr virus (EBV), we here report, for the first time, the identification of a snoRNA gene within a viral genome, designated as v-snoRNA1. This genetic element displays all hallmark sequence motifs of a canonical C/D box snoRNA, namely C/C′- as well as D/D′-boxes. The nucleolar localization of v-snoRNA1 was verified by in situ hybridisation of EBV-infected cells. We also confirmed binding of the three canonical snoRNA proteins, fibrillarin, Nop56 and Nop58, to v-snoRNA1. The C-box motif of v-snoRNA1 was shown to be crucial for the stability of the viral snoRNA; its selective deletion in the viral genome led to a complete down-regulation of v-snoRNA1 expression levels within EBV-infected B cells. We further provide evidence that v-snoRNA1 might serve as a miRNA-like precursor, which is processed into 24 nt sized RNA species, designated as v-snoRNA124pp. A potential target site of v-snoRNA124pp was identified within the 3′-UTR of BALF5 mRNA which encodes the viral DNA polymerase. V-snoRNA1 was found to be expressed in all investigated EBV-positive cell lines, including lymphoblastoid cell lines (LCL). Interestingly, induction of the lytic cycle markedly up-regulated expression levels of v-snoRNA1 up to 30-fold. By a computational approach, we identified a v-snoRNA1 homolog in the rhesus lymphocryptovirus genome. This evolutionary conservation suggests an important role of v-snoRNA1 during γ-herpesvirus infection.
The utility of rhesus monkey (Macaca mulatta) and other non-human primate models for preclinical testing of Leishmania candidate vaccines
Grimaldi Jr, Gabriel;
Memórias do Instituto Oswaldo Cruz , 2008, DOI: 10.1590/S0074-02762008000700002
Abstract: leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. given the urgent need to identify a safe and effective leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. this includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. old world monkey species (macaques, baboons, mandrills etc.) have the closest evolutionary relatedness to humans among the approachable animal models. the asian rhesus macaques (macaca mulatta) are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to leishmania and parasite-specific t-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. this review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.
Derivation of Rhesus Monkey Parthenogenetic Embryonic Stem Cells and Its MicroRNA Signature  [PDF]
Qiang Wei, Zhenghua Sun, Xiechao He, Tao Tan, Bin Lu, Xiangyu Guo, Bing Su, Weizhi Ji
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025052
Abstract: Parthenogenetic embryonic stem cells are considered as a promising resource for regeneration medicine and powerful tools for developmental biology. A lot of studies have revealed that embryonic stem cells have distinct microRNA expression pattern and these microRNAs play important roles in self-renewal and pluripotency of embryonic stem cells. However, few studies concern about microRNA expression pattern in parthenogenetic embryonic stem cells, especially in non-human primate—the ideal model species for human, largely due to the limited rhesus monkey parthenogenetic embryonic stem cells (rpESCs) available and lack of systematic analysis of the basics of rpESCs. Here, we derived two novel rpESCs lines and characterized their microRNA signature by Solexa deep sequencing. These two novel rpESCs shared many properties with other primate ESCs, including expression of pluripotent markers, capacity to generate derivatives representative of all three germ layers in vivo and in vitro, maintaining of euploid karyotype even after long culture. Additionally, lack of some paternally expressed imprinted genes and identity of Single-nucleotide Polymorphism (SNP) compare to their oocyte donors support their parthenogenesis origin. By characterizing their microRNA signature, we identified 91 novel microRNAs, except those are also detected in other primate ESCs. Moreover, these two novel rpESCs display a unique microRNA signature, comparing to their biparental counterpart ESCs. Then we analyzed X chromosome status in these two novel rpESCs; results suggested that one of them possesses two active X chromosomes, the other possesses only one active X chromosome liking biparental female embryonic stem cells. Taken together, our novel rpESCs provide a new alternative to existing rhesus monkey embryonic stem cells, microRNA information expands rhesus monkey microRNA data and may help understanding microRNA roles in pluripotency and parthenogenesis.
Cloning of a novel inhibin alpha cDNA from rhesus monkey testis
Daniel J Bernard, Teresa K Woodruff, Tony M Plant
Reproductive Biology and Endocrinology , 2004, DOI: 10.1186/1477-7827-2-71
Abstract: The subunit cDNAs were cloned by a combination of reverse transcriptase polymerase chain reaction (RT-PCR) and 5' rapid amplification of cDNA ends (RACE) RT-PCR from adult rhesus monkey testis RNA.Both the inhibin alpha and betaB subunit nucleotide and predicted protein sequences are highly conserved with other mammalian species, particularly with humans. During the course of these investigations, a novel inhibin alpha mRNA isoform was also identified. This form, referred to as rhesus monkey inhibin alpha-variant 2, appears to derive from both alternative transcription initiation as well as alternative splicing. rmInhibin alpha-variant 2 is comprised of a novel 5' exon (exon 0), which is spliced in-frame with exon 2 of the conventional inhibin alpha isoforms (variant 1). Exon 1 is skipped in its entirety such that the pro-alpha and part of the alpha N regions are not included in the predicted protein. rmInhibin alpha -variant 2 is of relatively low abundance and its biological function has not yet been ascertained.The data show that the predicted inhibin B protein is very similar between monkeys and humans. Therefore, studies in monkeys using recombinant human inhibins are likely to reflect actions of the homologous ligands. In addition, we have observed the first inhibin alpha subunit mRNA variant. It is possible that variants will be observed in other species as well and this may lead to novel insights into inhibin action.The inhibins are dimeric gonadal protein hormones that negatively regulate pituitary FSH synthesis and secretion [1,2]. Inhibins are comprised of an α subunit (inhibin α) and one of two inhibin β subunits (inhibin βA or inhibin βB). In adult male mammals, inhibin B (α-βB dimer) appears to be the primary circulating form of the hormone, whereas females produce both inhibin A and B and do so in discordant fashion across the reproductive cycle [3-15]. One exception to this general pattern is in rams, where inhibin A appears to be the primary circula
Small nucleolar RNAs (snoRNAs) as potential non-invasive biomarkers for early cancer detection  [cached]
Wen-Dan Chen,Xiao-Feng Zhu
Chinese Journal of Cancer , 2013, DOI: 10.5732/cjc.012.10132
Abstract: Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules, which are associated with specific proteins to form small nucleolar ribonucleoparticles. However, the function of snoRNAs in cancer still remains elusive. Recently, several independent lines of evidence have indicated that these ncRNAs might have crucial roles in controlling tumorigenesis, and snoRNAs could be potential biomarkers for cancer.
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