Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2

Takayuki Katoh1, Yuriko Sakaguchi, Kenjyo Miyauchi

  • 1Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.

Genes & Development
|February 26, 2009
PubMed

Insights

The enzyme GLD-2 adds a tail to microRNA-122 (miR-122), stabilizing it in the liver. This post-transcriptional modification by GLD-2 is crucial for maintaining mature miR-122 levels.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • MicroRNAs (miRNAs) regulate gene expression post-transcriptionally.
  • Some miRNAs undergo modifications like adenylation or uridylation at their 3' ends.
  • The liver-specific microRNA, miR-122, is critical for liver function.

Purpose of the Study:

  • To investigate the post-transcriptional regulation of miR-122.
  • To identify the enzyme responsible for 3'-terminal adenylation of miR-122.
  • To determine the role of this modification in miR-122 stability.

Main Methods:

  • Isolation of miR-122 from human hepatocytes and mouse livers.
  • Mass spectrometry to analyze miRNA variants.
  • Identification of the poly(A) polymerase GLD-2.
  • Analysis of miR-122 levels in GLD-2-null mice.

Main Results:

  • A variant of miR-122 with a 3'-terminal adenosine was identified.
  • GLD-2 was confirmed as the enzyme responsible for this adenylation.
  • GLD-2 deficiency led to significantly lower levels of mature miR-122 in mouse livers.
  • Levels of pre-miR-122 remained unaffected in GLD-2-null mice.

Conclusions:

  • 3'-terminal adenylation by GLD-2 is a key post-transcriptional process for miR-122.
  • This modification by GLD-2 is essential for the selective stabilization of mature miR-122 in the liver.
  • GLD-2 plays a critical role in maintaining hepatic miR-122 homeostasis.

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