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bioRxiv · 10.1101/093179

Genetic variation and RNA structure regulate microRNA biogenesis

Fernandez, N.·Cordiner, R. A.·Young, R. S.·Hug, N.·Macias, S.·Caceres, J. F.
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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 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 highlights that primary sequence determinants and RNA structure are key regulators of miRNA biogenesis.

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Fernandez, N., Cordiner, R. A., Young, R. S., Hug, N., Macias, S., Caceres, J. F.. 2016-12-12. Genetic variation and RNA structure regulate microRNA biogenesis. https://doi.org/10.1101/093179

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