5′ isomiR variation is of functional and evolutionary importance

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 Castellano, Gunter Meister, Robert M. Winston, Wei Cui, David Baulcombe, Nick J. Dibb

Research output: Contribution to journalArticle

92 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9424-9435
Number of pages12
JournalNucleic Acids Research
Volume42
Issue number14
DOIs
Publication statusPublished - 2014

Fingerprint

MicroRNAs
Genes
Argonaute Proteins
Fetal Stem Cells
Porifera
Computational Biology
Luciferases
Mesenchymal Stromal Cells
Northern Blotting
Databases

ASJC Scopus subject areas

  • Genetics

Cite this

Tan, G. C., Chan, E., Molnar, A., Sarkar, R., Alexieva, D., Isa, I. M., ... Dibb, N. J. (2014). 5′ isomiR variation is of functional and evolutionary importance. Nucleic Acids Research, 42(14), 9424-9435. https://doi.org/10.1093/nar/gku656

5′ isomiR variation is of functional and evolutionary importance. / Tan, Geok Chin; Chan, Elcie; Molnar, Attila; Sarkar, Rupa; Alexieva, Diana; Isa, Ihsan 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.

In: Nucleic Acids Research, Vol. 42, No. 14, 2014, p. 9424-9435.

Research output: Contribution to journalArticle

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 2014, '5′ isomiR variation is of functional and evolutionary importance', Nucleic Acids Research, vol. 42, no. 14, pp. 9424-9435. https://doi.org/10.1093/nar/gku656
Tan, Geok Chin ; Chan, Elcie ; Molnar, Attila ; Sarkar, Rupa ; Alexieva, Diana ; Isa, Ihsan 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. / 5′ isomiR variation is of functional and evolutionary importance. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 14. pp. 9424-9435.
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AU - Isa, Ihsan Mad

AU - Robinson, Sophie

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