5′ isomiR variation is of functional and evolutionary importance

Tan, Geok Chin, Chan, Elcie, Molnar, Attila, Sarkar, Rupa, Alexieva, Diana, Isa, Iihsan Mad, Robinson, Sophie, Zhang, Shuchen, Ellis, Peter, Langford, Cordelia F., Guillot, Pascale V., Chandrashekran, Anil, Fisk, Nick M., Castellano, Leandro, Meister, Gunter, Winston, Robert M., Cui, Wei, Baulcombe, David and Dibb, Nick J. (2014) 5′ isomiR variation is of functional and evolutionary importance. Nucleic Acids Research, 42 14: 9424-9435. doi:10.1093/nar/gku656

Author Tan, Geok Chin
Chan, Elcie
Molnar, Attila
Sarkar, Rupa
Alexieva, Diana
Isa, Iihsan Mad
Robinson, Sophie
Zhang, Shuchen
Ellis, Peter
Langford, Cordelia F.
Guillot, Pascale V.
Chandrashekran, Anil
Fisk, Nick M.
Castellano, Leandro
Meister, Gunter
Winston, Robert M.
Cui, Wei
Baulcombe, David
Dibb, Nick J.
Title 5′ isomiR variation is of functional and evolutionary importance
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 1362-4962
Publication date 2014-08-18
Year available 2014
Sub-type Article (original research)
DOI 10.1093/nar/gku656
Open Access Status DOI
Volume 42
Issue 14
Start page 9424
End page 9435
Total pages 12
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
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 ofmiRBase 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 32 times in Scopus Article | Citations
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