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SRSF3 recruits DROSHA to the basal junction of primary microRNAs

Kijun Kim1,2, Trung Duc Nguyen3,4, Shaohua Li3

  • 1Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea.

RNA (New York, N.Y.)
|April 5, 2018
PubMed

Insights

The Microprocessor complex initiates microRNA maturation. SRSF3 protein recruits DROSHA to specific RNA motifs, enhancing Microprocessor activity for efficient pri-miRNA processing.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • The Microprocessor complex, comprising DROSHA and DGCR8, processes primary microRNA (pri-miRNA) transcripts for miRNA maturation.
  • Pri-miRNAs often contain conserved RNA motifs like UG, UGU, and CNNC, which are crucial for Microprocessor interaction and orientation.

Purpose of the Study:

  • To elucidate the molecular mechanism by which SRSF3 (SRp20) stimulates Microprocessor activity in pri-miRNA processing.
  • To investigate the role of the CNNC motif in SRSF3-mediated enhancement of Microprocessor function.

Main Methods:

  • In vitro assays using engineered pri-miRNA substrates with varying CNNC motif locations.
  • Biochemical experiments to assess SRSF3 recruitment of DROSHA and Microprocessor activity.

Main Results:

  • SRSF3 recruits DROSHA to the basal junction of pri-miRNA in a CNNC-dependent manner.
  • This SRSF3-mediated recruitment significantly enhances Microprocessor activity.
  • The stimulatory effect of SRSF3 is dependent on the CNNC motif being positioned approximately 17 nucleotides from the Microprocessor cleavage site.

Conclusions:

  • SRSF3 enhances Microprocessor activity by recruiting DROSHA to a specific site on pri-miRNA, mediated by the CNNC motif.
  • The precise location of the CNNC motif is critical for this stimulatory mechanism, explaining its conserved positioning.
  • These findings provide a detailed molecular understanding of SRSF3's role in miRNA biogenesis.
Keywords:
DGCR8DROSHASRSF3microRNAmicroprocessor

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