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, Rigoutsos, I. 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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