Selective stabilization of mammalian microRNAs by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2.
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.
Katoh
Takayuki
T
Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan.
Sakaguchi
Yuriko
Y
Miyauchi
Kenjyo
K
Suzuki
Takeo
T
Kashiwabara
Shin-Ichi
S
Baba
Tadashi
T
Suzuki
Tsutomu
T
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000201:enzymology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism*
C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D011062:Polynucleotide Adenylyltransferase