Post-transcriptional regulation of BRCA2 through interactions with miR-19a and miR-19b

Our results suggest that BRCA2 is post-transcriptionally regulated by miR-19a and miR-19b, two members of the miR-17/92 cluster, and that these miRNA:BRCA2’s mRNA interactions affect the abundances of BRCA2’s mRNA and protein in a cell-specific context.1

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A subset of sporadic cancers has wild type BRCA2 and display defects in the homology-directed repair pathway, which is the hallmark of ‘BRCAness’. The mechanisms by which BRCAness arises are not fully understood but post-transcriptional regulation of BRCA2 gene expression by microRNAs (miRNAs) may contribute to this phenotype. Here, we examine the post-transcriptional effects that some members of the six-miRNA cluster known as the miR-17/92 cluster have on the abundance of BRCA2’s messenger RNA (mRNA) and protein. We discuss two interactions involving the miR-19a and miR-19b members of the cluster and the 3´UTR of BRCA2’s mRNA. We investigated these miRNA:mRNA interactions in 15 cell lines derived from pancreatic, breast, colon, and kidney tissue. We show that over-expression of these two miRNAs results in a concomitant decrease of BRCA2’s mRNA and protein expression in a subset of the tested cell lines. Additionally, using luciferase reporter assays we identified direct interactions between miR-19a/miR-19b and a miRNA response element (MRE) in BRCA2’s 3´UTR. Our results suggest that BRCA2 is subject to a complex post-transcriptional regulatory program that has specific dependencies on the genetic and phenotypic background of cell types.

References

  1. Mogilyansky, E, Clark, P, Quann, K, Zhou, H, Londin, E, Jing, Y et al.. Post-transcriptional Regulation of BRCA2 through Interactions with miR-19a and miR-19b. Front Genet. 2016;7 :143. doi: 10.3389/fgene.2016.00143. PubMed PMID:27630665 PubMed Central PMC5005319.

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