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5' isomiR variation is of functional and evolutionary importance

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posted on 2023-06-09, 13:55 authored by Geok Chin Tan, Elcie Chan, Attila Molnar, Rupa Sarkar, Diana Alexieva, Ihsan Mad Isa, Sophie Robinson, Shuchen Zhang, Peter Ellis, Cordelia F Langford, Pascale V Guillot, Anil Chandrashekran, Nick M Fisk, Leandro CastellanoLeandro Castellano, Gunter Meister, Robert M Winston, Wei Cui, David Baulcombe, Nick J Dibb
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nucleic Acids Research

ISSN

1362-4962

Publisher

Oxford University Press

Issue

14

Volume

42

Page range

9424-9435

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-06-25

First Open Access (FOA) Date

2018-06-25

First Compliant Deposit (FCD) Date

2018-06-25

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