BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex
BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex
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.
- Osaka Gakuin University Japan
- Osaka University Japan
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
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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