한빛사 논문
Haedong Kim1,2,4, Jimi Kim1,4, Sha Yu1, Young-Yoon Lee1,2, Junseong Park3, Ran Joo Choi3, Seon-Jin Yoon3, Seok-Gu Kang3, V. NarryKim1,2,5,*
1Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, Korea
3Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
4These authors contributed equally.
5Lead Contact
*Corresponding author
Abstract
Strand selection is a critical step in microRNA (miRNA) biogenesis. Although the dominant strand may change depending on cellular contexts, the molecular mechanism and physiological significance of such alternative strand selection (or “arm switching”) remain elusive. Here we find miR-324 to be one of the strongly regulated miRNAs by arm switching and identify the terminal uridylyl transferases TUT4 and TUT7 to be the key regulators. Uridylation of pre-miR-324 by TUT4/7 re-positions DICER on the pre-miRNA and shifts the cleavage site. This alternative processing produces a duplex with a different terminus from which the 3′ strand (3p) is selected instead of the 5′ strand (5p). In glioblastoma, the TUT4/7 and 3p levels are upregulated, whereas the 5p level is reduced. Manipulation of the strand ratio is sufficient to impair glioblastoma cell proliferation. This study uncovers a role of uridylation as a molecular switch in alternative strand selection and implicates its therapeutic potential.
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