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5 ' isomiR variation is of functional and evolutionary importance

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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