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A Mechanism for microRNA Arm Switching Regulated by Uridylation

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Title
A Mechanism for microRNA Arm Switching Regulated by Uridylation
Author(s)
Haedong Kim; Jimi Kim; Sha Yu; Young-Yoon Lee; Junseong Park; Ran Joo Choi; Seon-Jin Yoon; Seok-Gu Kang; V. Narry Kim
Subject
miRNAmiRNA biogenesisarm switchingstrand selectionmiRNA tailinguridylationTUTaseDICERmiR-324glioblastoma
Publication Date
2020-06
Journal
MOLECULAR CELL, v.78, no.6, pp.1224 - 1236
Publisher
CELL PRESS
Abstract
© 2020 Elsevier Inc. 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. Alternative strand selection (or “arm switching”) of miRNAs takes place depending on cellular context, but its molecular mechanism is unknown. Kim et al. identify miR-324 as one of the prominently regulated miRNAs by arm switching and reveal the mechanism involving uridylation
URI
https://pr.ibs.re.kr/handle/8788114/7836
DOI
10.1016/j.molcel.2020.04.030
ISSN
1097-2765
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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