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

Author:

Katoh Takayuki,Sakaguchi Yuriko,Miyauchi Kenjyo,Suzuki Takeo,Kashiwabara Shin-ichi,Baba Tadashi,Suzuki Tsutomu

Abstract

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.

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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