Journal
GENES & DEVELOPMENT
Volume 23, Issue 4, Pages 433-438Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1761509
Keywords
miRNA; miR-122; GLD-2; 3 ' adenylation; mass spectrometry
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Funding
- New Energy and Industrial Technology Development Organization ( NEDO)
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The steady-state levels of microRNAs ( miRNAs) and their activities are regulated by the post-transcriptional processes. It is known that 39 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.
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