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A Mechanism for microRNA Arm Switching Regulated by Uridylation

Authors
 Haedong Kim  ;  Jimi Kim  ;  Sha Yu  ;  Young-Yoon Lee  ;  Junseong Park  ;  Ran Joo Choi  ;  Seon-Jin Yoon  ;  Seok-Gu Kang  ;  V Narry Kim 
Citation
 MOLECULAR CELL, Vol.78(6) : 1224-1236.e5, 2020-06 
Journal Title
 MOLECULAR CELL 
ISSN
 1097-2765 
Issue Date
2020-06
Keywords
DICER ; TUTase ; arm switching ; glioblastoma ; miR-324 ; miRNA ; miRNA biogenesis ; miRNA tailing ; strand selection ; uridylation
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S1097276520302720
DOI
10.1016/j.molcel.2020.04.030
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179424
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