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Flexible pri-miRNA structures enable tunable production of 5' isomiRs

  1. Author:
    Bofill De Ros,Xavier [ORCID]
    Hong,Zhenyi
    Birkenfeld, Ben
    Alamo-Ortiz,Sarangelica
    Yang,Acong
    Dai,Lisheng
    Gu,Shuo [ORCID]

  2. Author Address

    RNA Mediated Gene Regulation Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA., Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.,
    1. Year: 2022
    2. Date: Jan
  2. Journal: RNA Biology
    1. 19
    2. 1
    3. Pages: 279-289
  4. Type of Article: Article
  1. Abstract:

    The Drosha cleavage of a pri-miRNA defines mature microRNA sequence. Drosha cleavage at alternative positions generates 5 39; isoforms (isomiRs) which have distinctive functions. To understand how pri-miRNA structures influence Drosha cleavage, we performed a systematic analysis of the maturation of endogenous pri-miRNAs and their variants both in vitro and in vivo. We show that in addition to previously known features, the overall structural flexibility of pri-miRNA impact Drosha cleavage fidelity. Internal loops and nearby G 183; U wobble pairs on the pri-miRNA stem induce the use of non-canonical cleavage sites by Drosha, resulting in 5 39; isomiR production. By analysing patient data deposited in the Cancer Genome Atlas, we provide evidence that alternative Drosha cleavage of pri-miRNAs is a tunable process that responds to the level of pri-miRNA-associated RNA-binding proteins. Together, our findings reveal that Drosha cleavage fidelity can be modulated by altering pri-miRNA structure, a potential mechanism underlying 5 39; isomiR biogenesis in tumours.[Figure: see text].

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External Sources

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  2. DOI: 10.1080/15476286.2022.2025680
  3. PMID: 35188062
  4. PMCID: PMC8865264

Library Notes

  1. Fiscal Year: FY2021-2022
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