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The Journal of Cell Biology
Article
License: CC BY NC SA
Data sources: UnpayWall
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PubMed Central
Other literature type . 2012
Data sources: PubMed Central
The Journal of Cell Biology
Article . 2012 . Peer-reviewed
Data sources: Crossref
The Journal of Experimental Medicine
Article . 2012 . Peer-reviewed
Data sources: Crossref
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BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex

Authors: Kawai, Shinji; Amano, Atsuo;

BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex

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.

Related Organizations
Keywords

Ribonuclease III, BRCA1 Protein, Neoplasm Proteins, DEAD-box RNA Helicases, DNA-Binding Proteins, MicroRNAs, HEK293 Cells, Gene Expression Regulation, Cell Line, Tumor, Humans, RNA Interference, Smad3 Protein, RNA, Small Interfering, Tumor Suppressor Protein p53, Research Articles, HeLa Cells

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
159
Top 1%
Top 10%
Top 1%
Green
hybrid
Related to Research communities
Cancer Research