Critical contribution of 3' non-seed base pairing to the in vivo function of the evolutionarily conserved let-7a microRNA

Ye Duan, Isana Veksler-Lublinsky, Victor Ambros

Research output: Contribution to journalArticlepeer-review

Abstract

Base pairing of the seed region (g2-g8) is essential for microRNA targeting; however, the in vivo function of the 3' non-seed region (g9-g22) is less well understood. Here, we report a systematic investigation of the in vivo roles of 3' non-seed nucleotides in microRNA let-7a, whose entire g9-g22 region is conserved among bilaterians. We find that the 3' non-seed sequence functionally distinguishes let-7a from its family paralogs. The complete pairing of g11-g16 is essential for let-7a to fully repress multiple key targets, including evolutionarily conserved lin-41, daf-12, and hbl-1. Nucleotides at g17-g22 are less critical but may compensate for mismatches in the g11-g16 region. Interestingly, a certain minimal complementarity to let-7a 3' non-seed sequence can be required even for sites with perfect seed pairing. These results provide evidence that the specific configurations of both seed and 3' non-seed base pairing can critically influence microRNA-mediated gene regulation in vivo.

Original languageEnglish
Article number110745
Number of pages16
JournalCell Reports
Volume39
Issue number4
DOIs
StatePublished - 26 Apr 2022

Keywords

  • 3′ non-seed pairing
  • CP: Molecular biology
  • daf-12
  • let-7
  • lin-41
  • microRNA
  • post-transcriptional regulation

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