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  5 ' isomiR variation is of functional and evolutionary importance

Tan, G. C., Chan, E., Molnar, A., Sarkar, R., Alexieva, D., Isa, I. M., et al. (2014). 5 ' isomiR variation is of functional and evolutionary importance. NUCLEIC ACIDS RESEARCH, 42(14), 9424-9435. doi:10.1093/nar/gku656.

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Tan, Geok Chin1, Author
Chan, Elcie1, Author
Molnar, Attila1, Author
Sarkar, Rupa1, Author
Alexieva, Diana1, Author
Isa, Ihsan Mad1, Author
Robinson, Sophie1, Author
Zhang, Shuchen1, Author
Ellis, Peter1, Author
Langford, Cordelia F.1, Author
Guillot, Pascale V.1, Author
Chandrashekran, Anil1, Author
Fisk, Nick M.1, Author
Castellano, Leandro1, Author
Meister, Gunter2, Author              
Winston, Robert M.1, Author
Cui, Wei1, Author
Baulcombe, David1, Author
Dibb, Nick J.1, Author
Affiliations:
1external, ou_persistent22              
2Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              

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Free keywords: EMBRYONIC STEM-CELLS; MICRORNA TARGETS; MESSENGER-RNAS; BIOGENESIS; EXPRESSION; REPRESSION; TRANSLATION; REPERTOIRE; GENOMICS; MIRNAS
 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.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000343219200055
DOI: 10.1093/nar/gku656
 Degree: -

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Title: NUCLEIC ACIDS RESEARCH
Source Genre: Journal
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Publ. Info: GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND : OXFORD UNIV PRESS
Pages: - Volume / Issue: 42 (14) Sequence Number: - Start / End Page: 9424 - 9435 Identifier: ISSN: 0305-1048