期刊
EMBO JOURNAL
卷 34, 期 13, 页码 1801-1815出版社
WILEY
DOI: 10.15252/embj.201590931
关键词
precursor microRNA; single-molecule fluorescence; TUT4 (ZCCHC11); TUT7 (ZCCHC6); uridylation
资金
- Institute for Basic Science from the Ministry of Science, ICT and Future Planning of Korea [IBS-R008-D1]
- BK21 Research Fellowships from the Ministry of Education of Korea
- Open Program of the Division for Earth and Life Sciences of the Netherlands Organization for Scientific Research [822.02.008]
- European Research Council [309509]
- European Research Council (ERC) [309509] Funding Source: European Research Council (ERC)
Terminal uridylyl transferases (TUTs) function as integral regulators of microRNA (miRNA) biogenesis. Using biochemistry, single-molecule, and deep sequencing techniques, we here investigate the mechanism by which human TUT7 (also known as ZCCHC6) recognizes and uridylates precursor miRNAs (pre-miRNAs) in the absence of Lin28. We find that the overhang of a pre-miRNA is the key structural element that is recognized by TUT7 and its paralogues, TUT4 (ZCCHC11) and TUT2 (GLD2/PAPD4). For group II pre-miRNAs, which have a 1-nt 3' overhang, TUT7 restores the canonical end structure (2-nt 3' overhang) through mono-uridylation,thereby promoting miRNA biogenesis. For pre-miRNAs where the 3' end is further recessed into the stem (as in 3' trimmed pre-miRNAs), TUT7 generates an oligo-U tail that leads to degradation. In contrast to Lin28-stimulated oligo-uridylation, which is processive, a distributive mode is employed by TUT7 for both mono- and oligo-uridylation in the absence of Lin28. The overhang length dictates the frequency (but not duration) of the TUT7-RNA interaction, thus explaining how TUT7 differentiates pre-miRNA species with different overhangs. Our study reveals dual roles and mechanisms of uridylation in repair and removal of defective pre-miRNAs.
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