Importance of miRNA stability and alternative primary miRNA isoforms in gene regulation during Drosophila development
Abstract
Mature microRNAs (miRNAs) are processed from primary transcripts (pri-miRNAs), and their expression is controlled at transcriptional and post-transcriptional levels. However, how regulation at multiple levels achieves precise control remains elusive. Using published and new datasets, we profile a time course of mature and pri-miRNAs in Drosophila embryos and reveal the dynamics of miRNA production and degradation as well as dynamic changes in pri-miRNA isoform selection. We found that 5' nucleotides influence stability of mature miRNAs. Furthermore, distinct half-lives of miRNAs from the mir-309 cluster shape their temporal expression patterns, and the importance of rapid degradation of the miRNAs in gene regulation is detected as distinct evolutionary signatures at the target sites in the transcriptome. Finally, we show that rapid degradation of miR-3/-309 may be important for regulation of the planar cell polarity pathway component Vang. Altogether, the results suggest that complex mechanisms regulate miRNA expression to support normal development.
Data availability
The small RNA library data produced for this study are deposited at NCBI SRA under SRP109269.
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Drosophila genetics reference panel 2VCF file for the DGRP Freeze 2.0 calls.
Article and author information
Author details
Funding
National Research Foundation Singapore (NRF2011NRF-NRFF001-042)
- Li Zhou
- Mandy YT Lim
- Katsutomo Okamura
National Institutes of Health (R01-GM083300)
- Diane Bortolamiol-Becet
Ministry of Education - Singapore (MOE2014-T2-2-039)
- Nicholas Tolwinski
National University of Singapore (R-154-000-536-133)
- Greg Tucker-Kellogg
National Institutes of Health (R01-NS083833)
- Diane Bortolamiol-Becet
National University of Singapore (R-154-000-562-112)
- Greg Tucker-Kellogg
National University of Singapore (R-154-000-582-651)
- Greg Tucker-Kellogg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Timothy W Nilsen, Case Western Reserve University, United States
Version history
- Received: May 16, 2018
- Accepted: July 4, 2018
- Accepted Manuscript published: July 19, 2018 (version 1)
- Version of Record published: July 30, 2018 (version 2)
Copyright
© 2018, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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