Hasler, Daniele and Meduri, Rajyalakshmi and Bak, Maciej and Lehmann, Gerhard and Heizinger, Leonhard and Wang, Xin and Li, Zhi-Tong and Sement, Francois M. and Bruckmann, Astrid and Dock-Bregeon, Anne-Catherine and Merkl, Rainer and Kalb, Reinhard and Grauer, Eva and Kunstmann, Erdmute and Zavolan, Mihaela and Liu, Mo-Fang and Fischer, Utz and Meister, Gunter and Fischer, Utz (2020) The Alazami Syndrome-Associated Protein LARP7 Guides U6 Small Nuclear RNA Modification and Contributes to Splicing Robustness. MOLECULAR CELL, 77 (5). 1014-+. ISSN 1097-2765, 1097-4164
Full text not available from this repository. (Request a copy)Abstract
The La-related protein 7 (LARP7) forms a complex with the nuclear 7SK RNA to regulate RNA polymerase II transcription. It has been implicated in cancer and the Alazami syndrome, a severe developmental disorder. Here, we report a so far unknown role of this protein in RNA modification. We show that LARP7 physically connects the spliceosomal U6 small nuclear RNA (snRNA) with a distinct subset of box C/D small nucleolar RNAs (snoRNAs) guiding U6 2'-O-methylation. Consistently, these modifications are severely compromised in the absence of LARP7. Although general splicing remains largely unaffected, transcriptome-wide analysis revealed perturbations in alternative splicing in LARP7-depleted cells. Importantly, we identified defects in 2'-O-methylation of the U6 snRNA in Alazami syndrome siblings carrying a LARP7 mutation. Our data identify LARP7 as a bridging factor for snoRNA-guided modification of the U6 snRNA and suggest that alterations in splicing fidelity contribute to the etiology of the Alazami syndrome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONCODING RNA; LA PROTEIN; CHAPERONE ACTIVITY; POLYMERASE-II; GENE; TRANSCRIPTION; RECOGNITION; BINDING; SNRNA; RIBONUCLEOPROTEIN; |
| 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 09:13 |
| Last Modified: | 29 Mar 2021 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44959 |
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