Wang, Xin and Li, Zhi-Tong and Yan, Yue and Lin, Penghui and Tang, Wei and Hasler, Daniele and Meduri, Rajyalakshmi and Li, Ye and Hua, Min-Min and Qi, Hui-Tao and Lin, Di-Hang and Shi, Hui-Juan and Hui, Jingyi and Li, Jinsong and Li, Dangsheng and Yang, Jian-Hua and Lin, Jinzhong and Meister, Gunter and Fischer, Utz and Liu, Mo-Fang (2020) LARP7-Mediated U6 snRNA Modification Ensures Splicing Fidelity and Spermatogenesis in Mice. MOLECULAR CELL, 77 (5). 999-+. ISSN 1097-2765, 1097-4164
Full text not available from this repository. (Request a copy)Abstract
U6 snRNA, as an essential component of the catalytic core of the pre-mRNA processing spliceosome, is heavily modified post-transcriptionally, with 2'-O-methylation being most common. The role of these modifications in pre-mRNA splicing as well as their physiological function in mammals have remained largely unclear. Here we report that the La-related protein LARP7 functions as a critical cofactor for 2'-O-methylation of U6 in mouse male germ cells. Mechanistically, LARP7 promotes U6 loading onto box C/D snoRNP, facilitating U6 2'-O-methylation by box C/D snoRNP. Importantly, ablation of LARP7 in the male germline causes defective U6 2'-O-methylation, massive alterations in pre-mRNA splicing, and spermatogenic failure in mice, which can be rescued by ectopic expression of wild-type LARP7 but not an U6-loading-deficient mutant LARP7. Our data uncover a novel role of LARP7 in regulating U6 2'-O-methylation and demonstrate the functional requirement of such modification for splicing fidelity and spermatogenesis in mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMALL NUCLEAR-RNA; IN-VITRO RECONSTITUTION; LA-RELATED PROTEINS; U2 SNRNA; M(6)A METHYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; 7SK SNRNP; TRANSCRIPTION; GENE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 09:10 |
| Last Modified: | 29 Mar 2021 09:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44958 |
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