Cargando…

Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay

Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Thus, for unknown reasons, oligodendrocytes may...

Descripción completa

Detalles Bibliográficos
Autores principales: Martin, Sophie, Allan, Kevin C., Pinkard, Otis, Sweet, Thomas, Tesar, Paul J., Coller, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411196/
https://www.ncbi.nlm.nih.gov/pubmed/36008413
http://dx.doi.org/10.1038/s41467-022-32766-3
_version_ 1784775264528498688
author Martin, Sophie
Allan, Kevin C.
Pinkard, Otis
Sweet, Thomas
Tesar, Paul J.
Coller, Jeff
author_facet Martin, Sophie
Allan, Kevin C.
Pinkard, Otis
Sweet, Thomas
Tesar, Paul J.
Coller, Jeff
author_sort Martin, Sophie
collection PubMed
description Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Thus, for unknown reasons, oligodendrocytes may be hypersensitive to perturbations in tRNA biology. In this study, we survey the tRNA transcriptome in the murine oligodendrocyte cell lineage and find that specific tRNAs are hypomodified in oligodendrocytes within or near the anticodon compared to oligodendrocyte progenitor cells (OPCs). This hypomodified state may be the result of differential expression of key modification enzymes during oligodendrocyte differentiation. Moreover, we observe a concomitant relationship between tRNA hypomodification and tRNA decoding potential; observing oligodendrocyte specific alterations in codon optimality-mediated mRNA decay and ribosome transit. Our results reveal that oligodendrocytes naturally maintain a delicate, hypersensitized tRNA/mRNA axis. We suggest this axis is a potential mediator of pathology in leukodystrophies and white matter disease when further insult to tRNA metabolism is introduced.
format Online
Article
Text
id pubmed-9411196
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-94111962022-08-27 Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay Martin, Sophie Allan, Kevin C. Pinkard, Otis Sweet, Thomas Tesar, Paul J. Coller, Jeff Nat Commun Article Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Thus, for unknown reasons, oligodendrocytes may be hypersensitive to perturbations in tRNA biology. In this study, we survey the tRNA transcriptome in the murine oligodendrocyte cell lineage and find that specific tRNAs are hypomodified in oligodendrocytes within or near the anticodon compared to oligodendrocyte progenitor cells (OPCs). This hypomodified state may be the result of differential expression of key modification enzymes during oligodendrocyte differentiation. Moreover, we observe a concomitant relationship between tRNA hypomodification and tRNA decoding potential; observing oligodendrocyte specific alterations in codon optimality-mediated mRNA decay and ribosome transit. Our results reveal that oligodendrocytes naturally maintain a delicate, hypersensitized tRNA/mRNA axis. We suggest this axis is a potential mediator of pathology in leukodystrophies and white matter disease when further insult to tRNA metabolism is introduced. Nature Publishing Group UK 2022-08-25 /pmc/articles/PMC9411196/ /pubmed/36008413 http://dx.doi.org/10.1038/s41467-022-32766-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Martin, Sophie
Allan, Kevin C.
Pinkard, Otis
Sweet, Thomas
Tesar, Paul J.
Coller, Jeff
Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title_full Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title_fullStr Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title_full_unstemmed Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title_short Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
title_sort oligodendrocyte differentiation alters trna modifications and codon optimality-mediated mrna decay
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411196/
https://www.ncbi.nlm.nih.gov/pubmed/36008413
http://dx.doi.org/10.1038/s41467-022-32766-3
work_keys_str_mv AT martinsophie oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay
AT allankevinc oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay
AT pinkardotis oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay
AT sweetthomas oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay
AT tesarpaulj oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay
AT collerjeff oligodendrocytedifferentiationalterstrnamodificationsandcodonoptimalitymediatedmrnadecay