Genetic Variation and RNA Structure Regulate MicroRNA Biogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2017 May 4

PMID 28466845

Citations 43

Authors

Noemi Fernandez

Ross A Cordiner

Robert S Young

Nele Hug

Sara Macias

Javier F Caceres

Affiliations

Soon will be listed here.

Abstract

MiRNA biogenesis is highly regulated at the post-transcriptional level; however, the role of sequence and secondary RNA structure in this process has not been extensively studied. A single G to A substitution present in the terminal loop of pri-mir-30c-1 in breast and gastric cancer patients had been previously described to result in increased levels of mature miRNA. Here, we report that this genetic variant directly affects Drosha-mediated processing of pri-mir-30c-1 in vitro and in cultured cells. Structural analysis of this variant revealed an altered RNA structure that facilitates the interaction with SRSF3, an SR protein family member that promotes pri-miRNA processing. Our results are compatible with a model whereby a genetic variant in pri-mir-30c-1 leads to a secondary RNA structure rearrangement that facilitates binding of SRSF3 resulting in increased levels of miR-30c. These data highlight that primary sequence determinants and RNA structure are key regulators of miRNA biogenesis.

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