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TUT 7 controls the fate of precursor micro RNA s by using three different uridylation mechanisms
Author(s) -
Kim Boseon,
Ha Minju,
Loeff Luuk,
Chang Hyeshik,
Simanshu Dhirendra K,
Li Sisi,
Fareh Mohamed,
Patel Dinshaw J,
Joo Chirlmin,
Kim V Narry
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201590931
Subject(s) - biogenesis , biology , microrna , lin28 , microbiology and biotechnology , rna , genetics , gene , embryonic stem cell , induced pluripotent stem cell
Terminal uridylyl transferases ( TUT s) function as integral regulators of micro RNA (mi RNA ) biogenesis. Using biochemistry, single‐molecule, and deep sequencing techniques, we here investigate the mechanism by which human TUT 7 (also known as ZCCHC 6) recognizes and uridylates precursor mi RNA s (pre‐mi RNA s) in the absence of Lin28. We find that the overhang of a pre‐mi RNA is the key structural element that is recognized by TUT 7 and its paralogues, TUT 4 ( ZCCHC 11) and TUT 2 ( GLD 2/ PAPD 4). For group II pre‐mi RNA s, which have a 1‐nt 3′ overhang, TUT 7 restores the canonical end structure (2‐nt 3′ overhang) through mono‐uridylation, thereby promoting mi RNA biogenesis. For pre‐mi RNA s where the 3′ end is further recessed into the stem (as in 3′ trimmed pre‐mi RNA s), TUT 7 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 TUT 7 for both mono‐ and oligo‐uridylation in the absence of Lin28. The overhang length dictates the frequency (but not duration) of the TUT 7‐ RNA interaction, thus explaining how TUT 7 differentiates pre‐mi RNA species with different overhangs. Our study reveals dual roles and mechanisms of uridylation in repair and removal of defective pre‐mi RNA s.