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10.1038/ncomms15114

http://scihub22266oqcxt.onion/10.1038/ncomms15114
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suck abstract from ncbi


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pmid28466845      Nat+Commun 2017 ; 8 (ä): ä
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  • Genetic variation and RNA structure regulate microRNA biogenesis #MMPMID28466845
  • Fernandez N; Cordiner RA; Young RS; Hug N; Macias S; Cáceres JF
  • Nat Commun 2017[]; 8 (ä): ä PMID28466845show ga
  • 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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