Article

Primate MicroRNAs miR-220 and miR-492 Lie within Processed Pseudogenes

Molecular Genetics and Bioinformatics, Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.
Journal of Heredity (Impact Factor: 2.09). 03/2006; 97(2):186-90. DOI: 10.1093/jhered/esj022
Source: PubMed

ABSTRACT

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 divergence. 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 candidates for miRNA incubators, it is unlikely that more than a very small percentage of new miRNAs arise this way.

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Available from: Eric J Devor
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    • "However, many of them are known to produce new, very often lineage-specific genes (Betran, Wang, et al. 2002; Marques et al. 2005; Svensson et al. 2006). They can also lead to new protein domains through fusion with other genes (Vinckenbosch et al. 2006; Baertsch et al. 2008), regulatory RNAs (Yano et al. 2004; Devor 2006), or other regulatory elements (Nozawa et al. 2005). Soares et al. (1985) discovered for the first time a functional retrosequence in the rodent genome in 1985. "

    Full-text · Dataset · Dec 2012
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    • "Within our miRNA gene dataset are three pseudogenes that represent novel miRNA genes in the tammar. Previous work has shown that two miRNAs in primates were derived from processed pseudogenes [30], although the incidence of this type of miRNA gene evolution is considered rare [19,30]. Thus, there has been lineage-specific selection on the hairpins found in these pseudogene transcripts, which we can infer is involved in tammar-specific gene regulation given the mature miRNAs observed from these loci. "
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    ABSTRACT: Background Small RNAs have proven to be essential regulatory molecules encoded within eukaryotic genomes. These short RNAs participate in a diverse array of cellular processes including gene regulation, chromatin dynamics and genome defense. The tammar wallaby, a marsupial mammal, is a powerful comparative model for studying the evolution of regulatory networks. As part of the genome sequencing initiative for the tammar, we have explored the evolution of each of the major classes of mammalian small RNAs in an Australian marsupial for the first time, including the first genome-scale analysis of the newest class of small RNAs, centromere repeat associated short interacting RNAs (crasiRNAs). Results Using next generation sequencing, we have characterized the major classes of small RNAs, micro (mi) RNAs, piwi interacting (pi) RNAs, and the centromere repeat associated short interacting (crasi) RNAs in the tammar. We examined each of these small RNA classes with respect to the newly assembled tammar wallaby genome for gene and repeat features, salient features that define their canonical sequences, and the constitution of both highly conserved and species-specific members. Using a combination of miRNA hairpin predictions and co-mapping with miRBase entries, we identified a highly conserved cluster of miRNA genes on the X chromosome in the tammar and a total of 94 other predicted miRNA producing genes. Mapping all miRNAs to the tammar genome and comparing target genes among tammar, mouse and human, we identified 163 conserved target genes. An additional nine genes were identified in tammar that do not have an orthologous miRNA target in human and likely represent novel miRNA-regulated genes in the tammar. A survey of the tammar gonadal piRNAs shows that these small RNAs are enriched in retroelements and carry members from both marsupial and tammar-specific repeat classes. Lastly, this study includes the first in-depth analyses of the newly discovered crasiRNAs. These small RNAs are derived largely from centromere-enriched retroelements, including a novel SINE. Conclusions This study encompasses the first analyses of the major classes of small RNAs for the newly completed tammar genome, validates preliminary annotations using deep sequencing and computational approaches, and provides a foundation for future work on tammar-specific as well as conserved, but previously unknown small RNA progenitors and targets identified herein. The characterization of new miRNA target genes and a unique profile for crasiRNAs has allowed for insight into multiple RNA mediated processes in the tammar, including gene regulation, species incompatibilities, centromere and chromosome function.
    Full-text · Article · Oct 2012 · BMC Genomics
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    • "However, many of them are known to produce new, very often lineage-specific genes (Betran, Wang, et al. 2002; Marques et al. 2005; Svensson et al. 2006). They can also lead to new protein domains through fusion with other genes (Vinckenbosch et al. 2006; Baertsch et al. 2008), regulatory RNAs (Yano et al. 2004; Devor 2006), or other regulatory elements (Nozawa et al. 2005). Soares et al. (1985) discovered for the first time a functional retrosequence in the rodent genome in 1985. "
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    ABSTRACT: Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes in order to identify "orphan" retrogenes, i.e. retrogenes that have replaced their progenitors. We located twenty five such candidates in the human genome. All of these genes were previously known and majority has been intensively studied. Despite this, they were never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes by their retrocopies has been taking place over the entire span of animal evolution. This process was often species-specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.
    Full-text · Article · Oct 2012 · Molecular Biology and Evolution
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