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RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex

Yukio Kawahara1, Boris Zinshteyn, Thimmaiah P Chendrimada

  • 1The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA. ykawahara@wistar.org

EMBO Reports
|June 30, 2007
PubMed

Insights

RNA editing of primary microRNA-151 (pri-miR-151) blocks its processing by Dicer. This adenosine to inosine (A --> I) RNA editing leads to the accumulation of pre-miR-151 RNAs, revealing a novel regulatory mechanism in microRNA biogenesis.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) regulate gene expression post-transcriptionally via RNA interference (RNAi).
  • miRNA biogenesis involves sequential processing of primary miRNA transcripts (pri-miRNAs) by Drosha and Dicer complexes.
  • Adenosine to inosine (A --> I) RNA editing can occur in pri-miRNAs, but its impact on miRNA processing remains largely unexplored.

Purpose of the Study:

  • To investigate the functional consequences of A --> I RNA editing on pri-miR-151 processing.
  • To elucidate the mechanism by which RNA editing affects miRNA biogenesis.

Main Methods:

  • Analysis of pri-miR-151 and its processed products in cells with and without RNA editing.
  • Biochemical assays to assess the interaction of edited pri-miRNAs with the Dicer-TRBP complex.
  • RNA sequencing and Northern blotting to quantify miRNA intermediates and mature miRNAs.

Main Results:

  • RNA editing of pri-miR-151 at specific sites leads to the accumulation of edited pre-miR-151 RNAs.
  • Edited pri-miR-151 is resistant to cleavage by the Dicer-TRBP complex.
  • A --> I conversion in the pre-miRNA structure impairs its interaction with Dicer-TRBP.

Conclusions:

  • A --> I RNA editing acts as a novel regulatory mechanism in miRNA biogenesis by inhibiting Dicer processing.
  • Specific RNA editing events in pri-miRNAs can dictate their fate and processing efficiency.
  • This finding expands our understanding of the interplay between RNA editing and RNA interference pathways.

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