BRCA1, the well-known breast cancer susceptibility gene, helps control the maturation of microRNAs, Kawai and Amano show. The finding suggests another way that BRCA1 mutations promote cancer.
The BRCA1 protein helps repair damaged DNA, and mutations in the gene raise the risk of breast and ovarian cancer and other tumor types. Some evidence implies that BRCA1 also takes part in the processing of microRNAs, the short RNA strands that modify gene expression. For example, microRNA levels are often abnormal in cells with BRCA1 mutations.
Kawai and Amano tested this idea. They found that boosting levels of the BRCA1 protein in cell lines increased the levels of several microRNAs. Deleting BRCA1 from cells had the opposite effect on the same microRNAs, all of which dwindle in cancer. BRCA1 had no impact on the levels of microRNAs whose abundance increases or remains the same in tumors, however.
BRCA1 bound to primary microRNA transcripts, Kawai and Amano found. The protein also interacted with the DROSHA processing complex and the proteins Smad3 and p53, which stimulate microRNA maturation. The results suggest that BRCA1 promotes the processing of specific microRNAs that might inhibit tumors. Whether BRCA1’s effects on microRNAs contribute to its roles in DNA repair remains to be seen.