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TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.
Chen, Lu; Roake, Caitlin M; Maccallini, Paolo; Bavasso, Francesca; Dehghannasiri, Roozbeh; Santonicola, Pamela; 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; Proietti, Gabriele; Wu, Yunming; Hammerschmidt, Matthias; De Pittà, Cristiano; Sales, Gabriele; Salzman, Julia; Pellizzoni, Livio; Wirth, Brunhilde; Di Schiavi, Elia; Gatti, Maurizio; Artandi, Steven E; Raffa, Grazia D.
Afiliação
  • Chen L; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Roake CM; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Maccallini P; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Bavasso F; Cancer Signaling and Epigenetics Program and Cancer Epigenetics Institute, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Dehghannasiri R; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Santonicola P; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Mendoza-Ferreira N; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Scatolini L; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Rizzuti L; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Esposito A; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
  • Gallotta I; Institute of Biosciences and BioResources, IBBR, CNR, Naples, Italy.
  • Francia S; Institute of Human Genetics, Center for Molecular Medicine Cologne, Institute for Genetics, University of Cologne, 50931 Cologne, Germany.
  • Cacchione S; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Galati A; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Palumbo V; Institute of Genetics and Biophysics, IGB-ABT, CNR, Naples, Italy.
  • Kobin MA; Institute of Genetics and Biophysics, IGB-ABT, CNR, Naples, Italy.
  • Tartaglia GG; IFOM-The FIRC Institute of Molecular Oncology, Milan, Italy.
  • Colantoni A; Istituto di Genetica Molecolare, CNR-Consiglio Nazionale delle Ricerche, Pavia, Italy.
  • Proietti G; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Wu Y; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Hammerschmidt M; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • De Pittà C; Cancer Signaling and Epigenetics Program and Cancer Epigenetics Institute, Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • Sales G; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Salzman J; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), Rome 00161, Italy.
  • Pellizzoni L; Center for Human Technology, Fondazione Istituto Italiano di Tecnologia (IIT), Genoa 16152, Italy.
  • Wirth B; Dipartimento di Biologia e Biotecnologie, Sapienza University of Rome, Rome, Italy.
  • Di Schiavi E; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), Rome 00161, Italy.
  • Gatti M; Center for Human Technology, Fondazione Istituto Italiano di Tecnologia (IIT), Genoa 16152, Italy.
  • Artandi SE; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), Rome 00161, Italy.
  • Raffa GD; Center for Human Technology, Fondazione Istituto Italiano di Tecnologia (IIT), Genoa 16152, Italy.
Nucleic Acids Res ; 50(21): 12400-12424, 2022 11 28.
Article em En | MEDLINE | ID: mdl-35947650
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Nuclear Pequeno / Metiltransferases / Neurônios Motores Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Nuclear Pequeno / Metiltransferases / Neurônios Motores Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article