IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32766-3.html
   My bibliography  Save this article

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

Author

Listed:
  • Sophie Martin

    (Johns Hopkins University School of Medicine)

  • Kevin C. Allan

    (Case Western Reserve University School of Medicine)

  • Otis Pinkard

    (Case Western Reserve University School of Medicine)

  • Thomas Sweet

    (Case Western Reserve University School of Medicine)

  • Paul J. Tesar

    (Case Western Reserve University School of Medicine)

  • Jeff Coller

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

Abstract

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.

Suggested Citation

  • Sophie Martin & Kevin C. Allan & Otis Pinkard & Thomas Sweet & Paul J. Tesar & Jeff Coller, 2022. "Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32766-3
    DOI: 10.1038/s41467-022-32766-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32766-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32766-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Joy Goffena & Frances Lefcort & Yongqing Zhang & Elin Lehrmann & Marta Chaverra & Jehremy Felig & Joseph Walters & Richard Buksch & Kevin G. Becker & Lynn George, 2018. "Elongator and codon bias regulate protein levels in mammalian peripheral neurons," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. J. Blaze & A. Navickas & H. L. Phillips & S. Heissel & A. Plaza-Jennings & S. Miglani & H. Asgharian & M. Foo & C. D. Katanski & C. P. Watkins & Z. T. Pennington & B. Javidfar & S. Espeso-Gil & B. Ros, 2021. "Author Correction: Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    3. Fadi J. Najm & Mayur Madhavan & Anita Zaremba & Elizabeth Shick & Robert T. Karl & Daniel C. Factor & Tyler E. Miller & Zachary S. Nevin & Christopher Kantor & Alex Sargent & Kevin L. Quick & Daniela , 2015. "Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo," Nature, Nature, vol. 522(7555), pages 216-220, June.
    4. J. Blaze & A. Navickas & H. L. Phillips & S. Heissel & A. Plaza-Jennings & S. Miglani & H. Asgharian & M. Foo & C. D. Katanski & C. P. Watkins & Z. T. Pennington & B. Javidfar & S. Espeso-Gil & B. Ros, 2021. "Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    5. Matthew S. Elitt & Lilianne Barbar & H. Elizabeth Shick & Berit E. Powers & Yuka Maeno-Hikichi & Mayur Madhavan & Kevin C. Allan & Baraa S. Nawash & Artur S. Gevorgyan & Stevephen Hung & Zachary S. Ne, 2020. "Suppression of proteolipid protein rescues Pelizaeus–Merzbacher disease," Nature, Nature, vol. 585(7825), pages 397-403, September.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rebeccah K. Stewart & Patrick Nguyen & Alain Laederach & Pelin C. Volkan & Jessica K. Sawyer & Donald T. Fox, 2024. "Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kunkun Zhang & Shaoxuan Chen & Qihua Yang & Shuanghui Guo & Qiang Chen & Zhixiong Liu & Li Li & Mengyun Jiang & Hongda Li & Jin Hu & Xu Pan & Wenbo Deng & Naian Xiao & Bo Wang & Zhan-xiang Wang & Lian, 2022. "The Oligodendrocyte Transcription Factor 2 OLIG2 regulates transcriptional repression during myelinogenesis in rodents," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Alexandra M. Cheney & Stephanann M. Costello & Nicholas V. Pinkham & Annie Waldum & Susan C. Broadaway & Maria Cotrina-Vidal & Marc Mergy & Brian Tripet & Douglas J. Kominsky & Heather M. Grifka-Walk , 2023. "Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Hsueh-Fu Wu & Wenxin Yu & Kenyi Saito-Diaz & Chia-Wei Huang & Joseph Carey & Frances Lefcort & Gerald W. Hart & Hong-Xiang Liu & Nadja Zeltner, 2022. "Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Laura J. Wagstaff & Nadine Bestard-Cuche & Maja Kaczmarek & Antonella Fidanza & Lorraine McNeil & Robin J. M. Franklin & Anna C. Williams, 2024. "CRISPR-edited human ES-derived oligodendrocyte progenitor cells improve remyelination in rodents," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Giampiero Porcu & Eliseo Serone & Velia De Nardis & Daniele Di Giandomenico & Giuseppe Lucisano & Marco Scardapane & Anna Poma & Antonella Ragnini-Wilson, 2015. "Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-22, December.
    6. Jaime Gonzalez Cardona & Matthew D Smith & Jingya Wang & Leslie Kirby & Jason T Schott & Todd Davidson & Jodi L Karnell & Katharine A Whartenby & Peter A Calabresi, 2019. "Quetiapine has an additive effect to triiodothyronine in inducing differentiation of oligodendrocyte precursor cells through induction of cholesterol biosynthesis," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-19, September.
    7. Debjit Khan & Iyappan Ramachandiran & Kommireddy Vasu & Arnab China & Krishnendu Khan & Fabio Cumbo & Dalia Halawani & Fulvia Terenzi & Isaac Zin & Briana Long & Gregory Costain & Susan Blaser & Amand, 2024. "Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m6A site accessibility," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    8. Rebeccah K. Stewart & Patrick Nguyen & Alain Laederach & Pelin C. Volkan & Jessica K. Sawyer & Donald T. Fox, 2024. "Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32766-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.