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      Evolution of the let-7 microRNA Family

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          Abstract

          The increase of bodyplan complexity in early bilaterian evolution is correlates with the advent and diversification of microRNAs. These small RNAs guide animal development by regulating temporal transitions in gene expression involved in cell fate choices and transitions between pluripotency and differentiation. One of the two known microRNAs whose origins date back before the bilaterian ancestor is mir-100. In Bilateria, it appears stably associated in polycistronic transcripts with let-7 and mir-125, two key regulators of development. In vertebrates, these three microRNA families have expanded to form a complex system of developmental regulators. In this contribution, we disentangle the evolutionary history of the let-7 locus, which was restructured independently in nematodes, platyhelminths, and deuterostomes. The foundation of a second let-7 locus in the common ancestor of vertebrates and urochordates predates the vertebrate-specific genome duplications, which then caused a rapid expansion of the let-7 family.

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          Most cited references48

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          An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

          Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
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            Fast folding and comparison of RNA secondary structures

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              Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells.

              MicroRNAs (miRNAs) are emerging as important, albeit poorly characterized, regulators of biological processes. Key to further elucidation of their roles is the generation of more complete lists of their numbers and expression changes in different cell states. Here, we report a new method for surveying the expression of small RNAs, including microRNAs, using Illumina sequencing technology. We also present a set of methods for annotating sequences deriving from known miRNAs, identifying variability in mature miRNA sequences, and identifying sequences belonging to previously unidentified miRNA genes. Application of this approach to RNA from human embryonic stem cells obtained before and after their differentiation into embryoid bodies revealed the sequences and expression levels of 334 known plus 104 novel miRNA genes. One hundred seventy-one known and 23 novel microRNA sequences exhibited significant expression differences between these two developmental states. Owing to the increased number of sequence reads, these libraries represent the deepest miRNA sampling to date, spanning nearly six orders of magnitude of expression. The predicted targets of those miRNAs enriched in either sample shared common features. Included among the high-ranked predicted gene targets are those implicated in differentiation, cell cycle control, programmed cell death, and transcriptional regulation.
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                Author and article information

                Journal
                RNA Biol
                RNA Biol
                RNA
                RNA Biology
                Landes Bioscience
                1547-6286
                1555-8584
                01 March 2012
                01 March 2012
                : 9
                : 3
                : 231-241
                Affiliations
                [1 ]Bioinformatics Group; Department of Computer Science and Interdisciplinary Center for Bioinformatics; University of Leipzig; Leipzig, Germany
                [2 ]Computational EvoDevo Group; Department of Computer Science and Interdisciplinary Center for Bioinformatics; University of Leipzig; Leipzig, Germany
                [3 ]LIFE - Leipzig Research Center for Civilization Diseases; Universität Leipzig; Leipzig, Germany
                [4 ]Max Planck Institute for Mathematics in the Sciences; Leipzig, Germany
                [5 ]Fraunhofer Institut für Zelltherapie und Immunologie – IZI; Leipzig, Germany
                [6 ]Department of Theoretical Chemistry; University of Vienna; Wien, Austria
                [7 ]Center for non-coding RNA in Technology and Health; University of Copenhagen; Frederiksberg C, Denmark
                [8 ]Santa Fe Institute; Santa Fe, NM USA
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Correspondence to: Peter F. Stadler, Email: studla@ 123456bioinf.uni-leipzig.de
                Article
                2011RNABIOL0201R 18974
                10.4161/rna.18974
                3384580
                22617875
                08738d0a-df2b-4618-8136-646a671a92dc
                Copyright © 2012 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                Categories
                RNA Families

                Molecular biology
                mirna evolution,mir-125,mir-100,let-7,microrna
                Molecular biology
                mirna evolution, mir-125, mir-100, let-7, microrna

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