Molecular evolution of a microRNA cluster.

by Athanasius F. Bompfünewerer , Christoph Flamm , Claudia Fried , Guido Fritzsch , Ivo L. Hofacker , Jörg Lehmann , Kristin Missal , Axel Mosig , Bettina Müller , Sonja J. Prohaska , Bärbel M. R. Stadler , Peter F. Stadler , Andrea Tanzer , Stefan Washietl , Christina Witwer , 2005

"... A plethora of new functions of non-coding RNAs have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and RNA modification to translational regulation. Ne ..."

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A plethora of new functions of non-coding RNAs have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and RNA modification to translational regulation. Nevertheless, very little is known about the evolution of this “Modern RNA World ” and its components. In this contribution we attempt to provide at least a cursory overview of the diversity of non-coding RNAs and functional RNA motifs in non-translated regions of regular messenger RNAs (mRNAs) with an emphasis on evolutionary questions. This survey is complemented by an in-depth analysis of examples from different classes of RNAs focusing mostly on their evolution in the vertebrate lineage. We present a survey of Y RNA genes in vertebrates, studies of the molecular evolution of the U7 snRNA, the snoRNAs E1/U17, E2, and E3, the Y RNA family, the let-7 microRNA family, and the mRNA-like evf-1 gene. We furthermore discuss the statistical distribution

Evidence for human microRNA-offset RNAs in small RNA sequencing data

by David Langenberger, Clara Bermudez-santana, Jana Hertel, Steve Hoffmann, Peter F. Stadler, Edificio Uriel Gutierrez Bogotá - Bioinformatics

"... MicroRNA-offset-RNAs (moRNAs) were recently detected as highly abundant class of small RNAs in a basal chordate. Using short read sequencing data we show here that moRNAs are also produced from human microRNA precursors, albeit at quite low expression levels. The expression levels of moRNAs are unre ..."

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MicroRNA-offset-RNAs (moRNAs) were recently detected as highly abundant class of small RNAs in a basal chordate. Using short read sequencing data we show here that moRNAs are also produced from human microRNA precursors, albeit at quite low expression levels. The expression levels of moRNAs are unrelated to those of the associated microRNAs. Surprisingly, microRNA precursors that also show moRNAs are typically evolutionarily old, comprising more than half of the miRNA families that were present in early Bilateria, while evidence for moRNAs was found only for a relative small fraction of miRNA families of recent origin. 1

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Primate microRNAs miR-220 and miR-492 lie within processed pseudogenes

by Eric J. Devor - J. Heredity , 2006

"... MicroRNAs (miRNAs) are a new and abundant class of small, noncoding RNAs. To date, the evolutionary history of most of these loci appears to be marked by duplication and di-vergence. The ultimate origin of miRNAs remains an open question. A survey of the genomic context of more than 300 human miRNA ..."

Abstract - Cited by 14 (0 self) - Add to MetaCart

MicroRNAs (miRNAs) are a new and abundant class of small, noncoding RNAs. To date, the evolutionary history of most of these loci appears to be marked by duplication and di-vergence. The ultimate origin of miRNAs remains an open question. A survey of the genomic context of more than 300 human miRNA loci revealed that two primate-specific miRNAs, miR-220 and miR-492, each lie within a processed pseudogene. In silico and in vitro examinations of these two loci suggest that this is a rare phenomenon requiring the juxtaposition of a specific combination of factors. Thus it appears that, while processed pseudogenes are good candi-dates for miRNA incubators, it is unlikely that more than a very small percentage of new miRNAs arise this way. MicroRNAs (miRNAs) are an abundant class of small, non-coding RNAs. First reported in Caenorhabditis elegans just over

Circulating microRNAs in hepatitis B virus–infected patients. J Viral Hepatitis.

by F Ji , B Yang , X Peng , H Ding , H You , P Tien , 2011

"... SUMMARY. MicroRNAs (miRNAs) are stably present in human serum. The relationship between circulating miRNAs and hepatitis B virus (HBV) infected liver disease has not been previously reported. Applied Biosystems array-based miRNA expression profiling was performed on pooled sera obtained from identi ..."

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SUMMARY. MicroRNAs (miRNAs) are stably present in human serum. The relationship between circulating miRNAs and hepatitis B virus (HBV) infected liver disease has not been previously reported. Applied Biosystems array-based miRNA expression profiling was performed on pooled sera obtained from identified groups of chronic asymptomatic carriers (ASC), patients with chronic hepatitis B (CHB) and HBVassociated acute-on-chronic liver failure (ACLF), as well as healthy controls (HC). Nine miRNAs were verified in more clinical samples by RT-PCR. The correlation between miRNAs expression and the relationship between miRNA levels and clinical characteristics was analysed. Results showed that circulating miRNAs were detected in all disease and control samples, and their numbers increased with symptom severity, from 37 in HC, 77 in ASC, 101 in CHB, to 135 in ACLF. The expression levels of most miRNAs were also up-regulated in HBV-infected patients when compared to HC. Expression of the liver-specific miR-122 was significantly up-regulated in HBV-infected patients. Concomitant regulation of miRNAs not in clusters was disrupted by HBV infection. However, such disruption was not observed for miRNAs in paralogous clusters. Furthermore, the level of miRNAs in the CHB serum was up-regulated most in hepatitis B e antigen-positive patients. The expression levels of miR-122 and miR-194 correlated negatively with the age of patients with CHB or ACLF. Functional analysis showed that miR-122 could inhibit HBV replication in Huh7 and HepG2 cells. In all, our study revealed that a number of miRNAs were differentially expressed during HBV infection and underscored the potential importance of miR-122 in the infection process.

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Review Coupling transcriptional and post‐transcriptional miRNA regulation in the control of cell fate

by Reut Shalgi, Ran Brosh, Moshe Oren, Yitzhak Pilpel, Varda Rotter

"... Copyright: © 2009 Shalgi et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Abstract: miRNAs function as a c ..."

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Copyright: © 2009 Shalgi et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Abstract: miRNAs function as a critical regulatory layer in development, differentiation, and the maintenance of cell fate. Depletion of miRNAs from embryonic stem cells impairs their differentiation capacity. Total elimination of miRNAs leads to premature senescence in normal cells and tissues through activation of the DNA‐damage checkpoint, whereas ablation of miRNAs in cancer cell lines results in an opposite effect, enhancing their tumorigenic potential. Here we compile evidence from the literature that point at miRNAs as key players in the maintenance of genomic integrity and proper cell fate. There is an apparent gap between our understanding of the subtle way by which miRNAs modulate protein levels, and their profound impact on cell fate. We propose that examining miRNAs in the context of the regulatory transcriptional and post‐ transcriptional networks they are embedded in may provide a broader view of their role in controlling cell fate. miRNAs are key regulators of cell fate miRNAs have emerged in the past decade as important players in numerous cellular and organismal processes in animals and plants [1]. Deletion of the Dicer gene,

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Clusters of microRNAs emerge by new hairpins in existing transcripts

by Antonio Marco , Maria Ninova , Matthew Ronshaugen , Sam Griffiths-Jones - Nucleic Acids Res , 2013

"... ABSTRACT Genetic linkage may result in the expression of multiple products from a polycistronic transcript, under the control of a single promoter. In animals, protein-coding polycistronic transcripts are rare. However, microRNAs are frequently clustered in the genomes of animals, and these cluster ..."

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ABSTRACT Genetic linkage may result in the expression of multiple products from a polycistronic transcript, under the control of a single promoter. In animals, protein-coding polycistronic transcripts are rare. However, microRNAs are frequently clustered in the genomes of animals, and these clusters are often transcribed as a single unit. The evolution of microRNA clusters has been the subject of much speculation, and a selective advantage of clusters of functionally related microRNAs is often proposed. However, the origin of microRNA clusters has not been so far explored. Here, we study the evolution of microRNA clusters in Drosophila melanogaster. We observed that the majority of microRNA clusters arose by the de novo formation of new microRNA-like hairpins in existing microRNA transcripts. Some clusters also emerged by tandem duplication of a single microRNA. Comparative genomics show that these clusters are unlikely to split or undergo rearrangements. We did not find any instances of clusters appearing by rearrangement of pre-existing microRNA genes. We propose a model for microRNA cluster evolution in which selection over one of the microRNAs in the cluster interferes with the evolution of the other linked microRNAs. Our analysis suggests that the study of microRNAs and small RNAs must consider linkage associations.

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EVOLUTIONARY GENOMICS OF microRNAs AND THEIR RELATIVES

by Andrea Tanzer, Markus Riester, Jana Hertel, Clara Isabel Bermudez-Santana, Jan Gorodkin, Ivo L. Hofacker, Peter F. Stadler , 2008

"... ..."

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Vascular smooth muscle-specific knockdown of the noncardiac form of the L-type calcium channel by microRNA-based short hairpin RNA as a potential antihypertensive therapy

by Sung W Rhee , Joseph R Stimers , Wenze Wang , Li Pang - J Pharmacol Exp Ther , 2009

"... ABSTRACT In different rodent models of hypertension, vascular voltagegated L-type calcium channel (Ca L ) current and vascular tone is increased because of increased expression of the noncardiac form of the Ca L (Ca v 1.2). The objective of this study was to develop a small interfering RNA (siRNA) ..."

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ABSTRACT In different rodent models of hypertension, vascular voltagegated L-type calcium channel (Ca L ) current and vascular tone is increased because of increased expression of the noncardiac form of the Ca L (Ca v 1.2). The objective of this study was to develop a small interfering RNA (siRNA) expression system against the noncardiac form of Ca v 1.2 to reduce its expression in vascular smooth muscle cells (VSMCs). siRNAs expressing plasmids and appropriate controls were constructed and first screened in human embryonic kidney (HEK) 293 cells cotransfected with a rat Ca v 1.2 expression vector. The most effective gene silencing was achieved with a modified mir-30a-based short hairpin RNA (shRNAmir) driven by the cytomegalovirus promoter. In A7r5 cells, a vascular smooth muscle cell line, two copies of shRNAmir driven by a chimeric VSMC-specific enhancer/promoter reduced endogenous Ca v 1.2 expression by 61% and decreased the Ca L current carried by barium by 47%. Moreover, the chimeric vascular smooth muscle-specific enhancer/promoter displayed almost no activity in non-VSMCs (PC-12 and HEK 293). Because the proposed siRNA was designed to only target the noncardiac form of Ca v 1.2, it did not affect the Ca L expression and function in cultured cardiomyocytes, even when driven by a stronger cytomegalovirus promoter. In conclusion, vascular Ca v 1.2 expression and function were effectively reduced by VSMC-specific delivery of the noncardiac form of Ca v 1.2 siRNA without similarly affecting cardiac Ca L expression and function. When coupled with a viral vector, this molecular intervention in vivo may provide a novel longterm vascular-specific gene therapy for hypertension. One hallmark finding in chronic hypertension is an anomalous constriction of small arteries and arterioles that is mediated by Ca 2ϩ influx through Ca L (Ca v 1.2). Ca v 1.2 expression is increased in the renal, mesenteric, and skeletal muscle circulations of different rodent models of hypertension, and the increased expression corresponds to a higher density of Ca L current and the development of anomalous vascular tone Ca v 1.2 is expressed in many tissues including heart, brain, lung, uterus, the gastrointestinal system, and VSMCs

Molecular evolution of a microRNA cluster. (2004)

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