PT  - JOURNAL ARTICLE
AU  - Noemi Fernandez
AU  - Ross A. Cordiner
AU  - Robert S. Young
AU  - Nele Hug
AU  - Sara Macias
AU  - Javier F. Cáceres
TI  - Genetic variation and RNA structure regulate microRNA biogenesis
AID  - 10.1101/093179
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 093179
4099  - http://biorxiv.org/content/early/2016/12/12/093179.short
4100  - http://biorxiv.org/content/early/2016/12/12/093179.full
AB  - 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.