Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation
- 15 February 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in RNA Biology
- Vol. 18 (11), 1905-1919
- https://doi.org/10.1080/15476286.2021.1881291
Abstract
RNA modifications are dynamic chemical entities that expand the RNA lexicon and regulate RNA fate. The most abundant modification present in mRNAs, N6-methyladenosine (m6A), 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 (m2,2G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNAAla(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.Keywords
This publication has 92 references indexed in Scilit:
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual DisabilityAmerican Journal of Human Genetics, 2012
- Accelerated Profile HMM SearchesPLoS Computational Biology, 2011
- A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing dataBioinformatics, 2011
- Biogenesis and function of nuclear bodiesTrends in Genetics, 2011
- REAP: A two minute cell fractionation methodBMC Research Notes, 2010
- New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0Systematic Biology, 2010
- Fast Mapping of Short Sequences with Mismatches, Insertions and Deletions Using Index StructuresPLoS Computational Biology, 2009
- RNA regulation of epigenetic processesBioEssays, 2009
- Variants of the elongator protein 3 ( ELP3 ) gene are associated with motor neuron degenerationHuman Molecular Genetics, 2008