AI Article Synopsis
- MiRNA biogenesis is tightly regulated after transcription, but the influence of RNA sequence and structure on this process is not well understood.
- A specific genetic variation (G to A substitution) in the pri-mir-30c-1 region has been linked to higher levels of mature miRNA in cancer patients, affecting how Drosha processes this RNA.
- The study shows that this variation changes RNA structure, promoting the binding of SRSF3, which enhances the processing of pri-miRNA, thus emphasizing the importance of RNA structure in miRNA biogenesis.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418625 | PMC |
| http://dx.doi.org/10.1038/ncomms15114 | DOI Listing |
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