Chen, Lu ORCID: 0000-0002-4571-7975, Roake, Caitlin M., Maccallini, Paolo, Bavasso, Francesca, Dehghannasiri, Roozbeh, Santonicola, Pamela ORCID: 0000-0002-4094-9996, Mendoza-Ferreira, Natalia, Scatolini, Livia, Rizzuti, Ludovico, Esposito, Alessandro, Gallotta, Ivan, Francia, Sofia, Cacchione, Stefano, Galati, Alessandra, Palumbo, Valeria, Kobin, Marie A., Tartaglia, Gian Gaetano, Colantoni, Alessio ORCID: 0000-0001-7402-0176, Proietti, Gabriele, Wu, Yunming, Hammerschmidt, Matthias, De Pitta, Cristiano ORCID: 0000-0001-8013-8162, Sales, Gabriele, Salzman, Julia, Pellizzoni, Livio, Wirth, Brunhilde, Di Schiavi, Elia ORCID: 0000-0002-8179-6666, Gatti, Maurizio, Artandi, Steven E. and Raffa, Grazia D. (2022). TGS1 impacts snRNA 3 '-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration. Nucleic Acids Res., 50 (21). S. 12400 - 12425. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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Abstract

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5'-monomethylguanosine cap of small nuclear RNAs (snRNAs) to a trimethylguanosine cap. Here, we show that loss of TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results in neurological phenotypes similar to those caused by survival motor neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3' tails that are often uridylated. snRNAs with defective 3' terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Chen, LuUNSPECIFIEDorcid.org/0000-0002-4571-7975UNSPECIFIED
Roake, Caitlin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maccallini, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bavasso, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dehghannasiri, RoozbehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santonicola, PamelaUNSPECIFIEDorcid.org/0000-0002-4094-9996UNSPECIFIED
Mendoza-Ferreira, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scatolini, LiviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rizzuti, LudovicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esposito, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallotta, IvanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Francia, SofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cacchione, StefanoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galati, AlessandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palumbo, ValeriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobin, Marie A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tartaglia, Gian GaetanoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Colantoni, AlessioUNSPECIFIEDorcid.org/0000-0001-7402-0176UNSPECIFIED
Proietti, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, YunmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammerschmidt, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Pitta, CristianoUNSPECIFIEDorcid.org/0000-0001-8013-8162UNSPECIFIED
Sales, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salzman, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pellizzoni, LivioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirth, BrunhildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Schiavi, EliaUNSPECIFIEDorcid.org/0000-0002-8179-6666UNSPECIFIED
Gatti, MaurizioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artandi, Steven E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raffa, Grazia D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-693450
DOI: 10.1093/nar/gkac659
Journal or Publication Title: Nucleic Acids Res.
Volume: 50
Number: 21
Page Range: S. 12400 - 12425
Date: 2022
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1362-4962
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SPINAL MUSCULAR-ATROPHY; SMALL-NUCLEAR-RNA; CAENORHABDITIS-ELEGANS; POLYMERASE-II; SMN COMPLEX; C-ELEGANS; 3' END; GENE-EXPRESSION; MOUSE-MODEL; KNOCK-DOWNMultiple languages
Biochemistry & Molecular BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69345

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