Details

Autor(en) / Beteiligte

• Kim, Haedong
• Kim, Jimi
• Yu, Sha
• Lee, Young-Yoon
• Park, Junseong
• Choi, Ran Joo
• Yoon, Seon-Jin
• Kang, Seok-Gu
• Kim, V. Narry

Titel

A Mechanism for microRNA Arm Switching Regulated by Uridylation

Ist Teil von

• Molecular cell, 2020-06, Vol.78 (6), p.1224-1236.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Arm switching of miR-324 is regulated by terminal uridylyl transferases•TUT4 and TUT7 uridylate pre-miR-324, resulting in alternative processing by DICER•The altered cleavage leads to selection of the 3p strand instead of the 5p strand•Perturbation of the miR-324 arm usage disrupts glioblastoma cell proliferation 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.