RRC ID 68669
Author Kawai S, Amano A.
Title BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex.
Journal J Cell Biol
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.
Volume 197(2)
Pages 201-8
Published 2012-4-16
DOI 10.1083/jcb.201110008
PII jcb.201110008
PMID 22492723
PMC PMC3328391
MeSH BRCA1 Protein / metabolism* Cell Line, Tumor DEAD-box RNA Helicases / metabolism DNA-Binding Proteins / metabolism Gene Expression Regulation HEK293 Cells HeLa Cells Humans MicroRNAs / biosynthesis* MicroRNAs / metabolism Neoplasm Proteins / metabolism RNA Interference RNA, Small Interfering Ribonuclease III / metabolism* Smad3 Protein / metabolism Tumor Suppressor Protein p53 / metabolism
IF 8.811
Human and Animal Cells HeLa(RCB0007) 293(RCB1637) MG-63(RCB1890)