1. Chromosomes and Gene Expression
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Importance of miRNA stability and alternative primary miRNA isoforms in gene regulation during Drosophila development

  1. Li Zhou
  2. Mandy YT Lim
  3. Prameet Kaur
  4. Abil Saj
  5. Diane Bortolamiol-Becet
  6. Vikneswaran Gopal
  7. Nicholas Tolwinski
  8. Greg Tucker-Kellogg
  9. Katsutomo Okamura  Is a corresponding author
  1. National University of Singapore, Singapore
  2. Yale-NUS College, Singapore
  3. Genome Institute of Singapore, Singapore
  4. Sloan-Kettering Institute, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2018;7:e38389 doi: 10.7554/eLife.38389

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Li Zhou

    Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  2. Mandy YT Lim

    Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Prameet Kaur

    Division of Science, Yale-NUS College, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Abil Saj

    Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Diane Bortolamiol-Becet

    Department of Developmental Biology, Sloan-Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Vikneswaran Gopal

    Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  7. Nicholas Tolwinski

    Department of Biological Sciences, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  8. Greg Tucker-Kellogg

    Department of Biological Sciences, National University of Singapore, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  9. Katsutomo Okamura

    Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore
    For correspondence
    okamurak@tll.org.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8316-0960

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

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

  1. Received: May 16, 2018
  2. Accepted: July 4, 2018
  3. Accepted Manuscript published: July 19, 2018 (version 1)
  4. 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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