Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation.

Autor: Jonkhout N; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain., Cruciani S; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain.; University Pompeu Fabra (UPF), Barcelona, Spain., Santos Vieira HG; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain., Tran J; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Liu H; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain., Liu G; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; Current Address: School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China., Pickford R; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia., Kaczorowski D; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Franco GR; Departamento De Bioquímica E Imunologia, Universidade Federal De Minas Gerais,Belo Horizonte,Minas Gerais, Brazil., Vauti F; Division of Cellular & Molecular Neurobiology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany., Camacho N; Institute for Research in Biomedicine, Barcelona, Catalonia, Spain., Abedini SS; Department of Genetics, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Najmabadi H; Department of Genetics, Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.; Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran., Ribas de Pouplana L; Institute for Research in Biomedicine, Barcelona, Catalonia, Spain.; Catalan Institution for Research and Advanced Studies, Barcelona, Catalonia, Spain., Christ D; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia., Schonrock N; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Mattick JS; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia., Novoa EM; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain.; University Pompeu Fabra (UPF), Barcelona, Spain.
Jazyk: angličtina
Zdroj: RNA biology [RNA Biol] 2021 Nov; Vol. 18 (11), pp. 1905-1919. Date of Electronic Publication: 2021 Feb 15.
DOI: 10.1080/15476286.2021.1881291
Abstrakt: RNA modifications are dynamic chemical entities that expand the RNA lexicon and regulate RNA fate. The most abundant modification present in mRNAs, N6-methyladenosine (m 6 A), has been implicated in neurogenesis and memory formation. However, whether additional RNA modifications may be playing a role in neuronal functions and in response to environmental queues is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1- like (TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m 2,2 G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNA Ala (AGC) isodecoders at position 26. Using a cellular in vitro model that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes may play a role in neuronal plasticity and transmission of information, presumably by addressing new targets.
Databáze: MEDLINE
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