TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
28 11 2022
28 11 2022
Historique:
accepted:
21
07
2022
received:
29
06
2022
pubmed:
11
8
2022
medline:
21
12
2022
entrez:
10
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35947650
pii: 6659874
doi: 10.1093/nar/gkac659
pmc: PMC9757054
doi:
Substances chimiques
RNA, Small Nuclear
0
trimethylguanosine synthase
EC 2.1.1.-
Methyltransferases
EC 2.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12400-12424Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102451
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197563
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056575
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
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