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BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex

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Kawai, Shinji, Amano, Atsuo·2012·Journal of Cell Biology

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. miRNA maturation is controlled by the DROSHA microprocessor complex. However, the detailed mechanism of miRNA biogenesis remains unclear. We show that the tumor suppressor breast cancer 1 (BRCA1) accelerates the processing of miRNA primary transcripts. BRCA1 increased the expressions of both precursor and mature forms of let-7a-1, miR-16-1, miR-145, and miR-34a. In addition, this tumor suppressor was shown to be directly associated with DROSHA and DDX5 of the DROSHA microprocessor complex, and it interacted with Smad3, p53, and DHX9 RNA helicase. We also found that BRCA1 recognizes the RNA secondary structure and directly binds with primary transcripts of miRNAs via a DNA-binding domain. Together, these results suggest that BRCA1 regulates miRNA biogenesis via the DROSHA microprocessor complex and Smad3/p53/DHX9. Our findings also indicate novel functions of BRCA1 in miRNA biogenesis, which may be linked to its tumor suppressor mechanism and maintenance of genomic stability.

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Research works printed but not linked: 28

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Metadata

Authors
Kawai, S., & Amano, A.
Venue
Journal of Cell Biology
Published
2012-04-09
Volume
197
Issue
2
Pages
201-208
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2116005916
Cited by
182
References
2
FWCI
6.41
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex. https://app.cochat.ai/papers/10.1083/jcb.201110008
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Kawai, S., & Amano, A. (2012). BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex. Journal of Cell Biology. https://doi.org/10.1083/jcb.201110008

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