Skip to main content
 

Structural Differences Between Pri-miRNA Paralogs Promotes Alternative Drosha Cleavage and Expands Target Repertoires

Wednesday, September 12, 2018 — Poster Session I

12:00 p.m. – 1:30 p.m.
FAES Terrace
NCI
GEN-2

Authors

  • X Bofill-De Ros
  • WK Kasprzak
  • Y Bhandari
  • L Fan
  • Q Cavanaugh
  • M Jiang
  • L Dai
  • A Yang
  • TJ Shao
  • BA Shapiro
  • YX Wang
  • S Gu

Abstract

MicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream processing and mature miRNA target specificity. To understand how pri-miRNA sequence and structure influence Drosha cleavage, we studied the maturation of three pri-miR-9 paralogs, which encode the same mature miRNA but differ in the surrounding scaffold. We show that pri-miR-9-1 has a unique Drosha cleavage profile due to its distorted and flexible stem structure. Cleavage of pri-miR-9-1, but not pri-miR-9-2 or pri-miR-9-3, generates an alternative-miR-9 with a shifted seed sequence that expands the scope of its target RNAs. Analyses of low grade glioma patient samples indicate that the alternative-miR-9 plays a distinct role in preventing tumor progression. To generalize our model, we provide evidence that distortion of pri-miRNA stems correlates with Drosha cleavage at non-canonical sites. Our studies reveal that pri-miRNA paralogs can have distinct functions via differential Drosha processing.

Category: Genetics and Genomics