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BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex
Open accessAbstract
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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“…forms a large multiprotein complex known as the BRCA1-associated genome surveillance complex with DNA damage sensors and other tumor suppressors (Wang et al., 2000), whereas it also interacts with RNA polymerase II and histone deacetylase complexes, and is involved in transcriptional control…”
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Cited by
MicroRNA biogenesis pathways in cancer
Lin, S., & Gregory, R. I. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3932 · Cited by 2,112
Regulation of microRNA biogenesis and its crosstalk with other cellular pathways
Treiber, T., Treiber, N., & Meister, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0059-1 · Cited by 1,252
BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing
Zhao, W., Steinfeld, J. B., Liang, F., Chen, X., Maranon, D. G., Jian Ma, C., Kwon, Y., Rao, T., Wang, W., Sheng, C., et al. (2017) · Nature · doi:10.1038/nature24060 · Cited by 393
Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer
Mori, M., Triboulet, R., Mohseni, M., Schlegelmilch, K., Shrestha, K., Camargo, F. D., & Gregory, R. I. (2014) · Cell · doi:10.1016/j.cell.2013.12.043 · Cited by 335
Circulating miRNAs: Roles in cancer diagnosis, prognosis and therapy
Cheng, G. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.001 · Cited by 334
Metadata
- Authors
- Kawai, S., & Amano, A.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- 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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