Regulation of large number of weak targets - New insights from twin-microRNAs

Zhao, Y., Lin, P., Liufu, Z., Yang, H., Lyu, Y., Shen, X., Wu, C. I., Tang, T. (April 2018) Regulation of large number of weak targets - New insights from twin-microRNAs. Genome Biology and Evolution, 10 (5). pp. 1255-1264. ISSN 17596653 (ISSN)

URL: https://www.ncbi.nlm.nih.gov/pubmed/29688430
DOI: 10.1093/gbe/evy079

Abstract

Each animalmicroRNA (miRNA) targetsmany genes for repression. Down-regulation ofmost of these targets isweak and has no detectable individual phenotypic effect.Whether this extensive weak repression is biologically relevant is a central issue in the debate on miRNA functionality. In the "small (target) pool" view, weak repression is nonfunctional and should be gradually removed during evolution. However, since the selective advantage of removing individual targets is small, testing this hypothesis is a challenge.We propose a novel approach by using miRNAs we call twin-miRs, which produce twomature products from the hairpin of the same miRNA precursor. Loss of the minor miR partner would affect all its targets and thus could be visible to selection. Since the minor miRs repress all their targets weakly, the "small pool" hypothesis would predict the elimination of twin-miRs over time. Surveying and sequencing 45 small RNA libraries in Drosophila, we found that nearly 40%ofmiRNAs produce twin-miRs. Theminor forms are expressed in nontrivial abundance and repress their targetsweakly. Interestingly, twin-miRs are often evolutionarily old, highly conserved, and comparable to solo-miRs in expression. Since there is no measurable trend toward reduction in target pool size, we conclude that at least some of the weak repression interactions are functional. A companion study using the May-Wigner theory of network stability suggests that distributed weak repression cumulatively contributes to stability of gene regulatory networks. © The Author(s) 2018.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Depositing User: Matthew Dunn
Date: 1 April 2018
Date Deposited: 30 Aug 2018 18:50
Last Modified: 30 Aug 2018 18:50
PMCID: PMC5963297
Related URLs:
URI: https://repository.cshl.edu/id/eprint/37177

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