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5' Isomir Variation Is Of Functional And Evolutionary Importance
Date : 02/07/2014
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Uploaded by : Sophie
Uploaded on : 02/07/2014
Subject : Biology
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 transcri pt 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.
This resource was uploaded by: Sophie