Genetic variation and RNA structure regulate microRNA biogenesis

Noemí Fernandez, Ross A. Cordiner, Robert S. Young, Nele Hug, Sara Macias, Javier F. Cáceres

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number15114
Number of pages12
JournalNature Communications
Volume8
Early online date3 May 2017
DOIs
Publication statusPublished - 3 May 2017

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