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10.15252/embj.201590931

http://scihub22266oqcxt.onion/10.15252/embj.201590931
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C4516432!4516432!25979828
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suck abstract from ncbi


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pmid25979828      EMBO+J 2015 ; 34 (13): 1801-15
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  • TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms #MMPMID25979828
  • Kim B; Ha M; Loeff L; Chang H; Simanshu DK; Li S; Fareh M; Patel DJ; Joo C; Kim VN
  • EMBO J 2015[Jul]; 34 (13): 1801-15 PMID25979828show ga
  • 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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