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

Genes Dev. 2009 Feb 15;23(4):433-8. doi: 10.1101/gad.1761509.


The steady-state levels of microRNAs (miRNAs) and their activities are regulated by the post-transcriptional processes. It is known that 3' ends of several miRNAs undergo post-dicing adenylation or uridylation. We isolated the liver-specific miR-122 from human hepatocytes and mouse livers. Direct analysis by mass spectrometry revealed that one variant of miR-122 has a 3'-terminal adenosine that is introduced after processing by Dicer. We identified GLD-2, which is a regulatory cytoplasmic poly(A) polymerase, as responsible for the 3'-terminal adenylation of miR-122 after unwinding of the miR-122/miR-122* duplex. In livers from GLD-2-null mice, the steady-state level of the mature form of miR-122 was specifically lower than in heterozygous mice, whereas no reduction of pre-miR-122 was observed, demonstrating that 3'-terminal adenylation by GLD-2 is required for the selective stabilization of miR-122 in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cytoplasm / enzymology*
  • Humans
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Polynucleotide Adenylyltransferase / metabolism*


  • MIRN122 microRNA, human
  • MicroRNAs
  • Polynucleotide Adenylyltransferase