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5 ' isomiR variation is of functional and evolutionary importance
File | Description | Size | Format | |
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5' isomiR variation is of functional and evolutionary importance.pdf | Published version | 2.29 MB | Adobe PDF | View/Open |
Title: | 5 ' isomiR variation is of functional and evolutionary importance |
Authors: | Tan, GC Chan, E Molnar, A Sarkar, R Alexieva, D Isa, IM Robinson, S Zhang, S Ellis, P Langford, CF Guillot, PV Chandrashekran, A Fisk, NM Castellano, L Meister, G Winston, RM Cui, W Baulcombe, D Dibb, NJ |
Item Type: | Journal Article |
Abstract: | We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3 and/or 5 end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5 differences and in support of this we report that a 5 isomiR-9–1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5 isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes. INT |
Issue Date: | 18-Aug-2014 |
Date of Acceptance: | 8-Jul-2014 |
URI: | http://hdl.handle.net/10044/1/26890 |
DOI: | 10.1093/nar/gku656 |
ISSN: | 1362-4962 |
Publisher: | Oxford University Press (OUP) |
Start Page: | 9424 |
End Page: | 9435 |
Journal / Book Title: | Nucleic Acids Research |
Volume: | 42 |
Issue: | 14 |
Copyright Statement: | © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology EMBRYONIC STEM-CELLS MICRORNA TARGETS MESSENGER-RNAS BIOGENESIS EXPRESSION REPRESSION TRANSLATION REPERTOIRE GENOMICS MIRNAS Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology MICRORNA TARGETS MESSENGER-RNAS BIOGENESIS EXPRESSION REPRESSION REPERTOIRE MIRNAS Animals Argonaute Proteins Cell Line Evolution, Molecular Humans Mice MicroRNAs RNA Precursors RNA, Messenger Stem Cells Cell Line Stem Cells Animals Humans Mice MicroRNAs RNA Precursors RNA, Messenger Evolution, Molecular Argonaute Proteins 05 Environmental Sciences 06 Biological Sciences 08 Information and Computing Sciences Developmental Biology |
Publication Status: | Published |
Online Publication Date: | 2014-07-23 |
Appears in Collections: | Department of Metabolism, Digestion and Reproduction Department of Surgery and Cancer Faculty of Medicine |