RT Journal Article SR Electronic T1 Genetic variation and RNA structure regulate microRNA biogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 093179 DO 10.1101/093179 A1 Noemi Fernandez A1 Ross A. Cordiner A1 Robert S. Young A1 Nele Hug A1 Sara Macias A1 Javier F. Cáceres YR 2016 UL http://biorxiv.org/content/early/2016/12/12/093179.abstract 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.