TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms
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Boseon Kim [3] ; Minju Ha [3] ; Luuk Loeff [2] ; Hyeshik Chang [3] ; Dhirendra K Simanshu [1] ; Sisi Li [1] ; Mohamed Fareh [2] ; Dinshaw J Patel [1] ; Chirlmin Joo [2] ; V Narry Kim [3]
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[1] Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
Estados Unidos
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[2] Delft University of Technology
Delft University of Technology
Países Bajos
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[3] Seoul National University
Seoul National University
Corea del Sur
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- Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 34, Nº. 13, 2015, págs. 1801-1815
- Idioma: inglés
- Enlaces
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Resumen
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.
