IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29786-4.html
   My bibliography  Save this article

Multilayered regulations of alternative splicing, NMD, and protein stability control temporal induction and tissue-specific expression of TRIM46 during axon formation

Author

Listed:
  • John K. Vuong

    (University of California, Riverside)

  • Volkan Ergin

    (University of California, Riverside)

  • Liang Chen

    (University of Southern California)

  • Sika Zheng

    (University of California, Riverside
    Center for RNA Biology and Medicine, University of California Riverside)

Abstract

The gene regulation underlying axon formation and its exclusiveness to neurons remains elusive. TRIM46 is postulated to determine axonal fate. We show Trim46 mRNA is expressed before axonogenesis, but TRIM46 protein level is inhibited by alternative splicing of two cassette exons coupled separately to stability controls of Trim46 mRNA and proteins, effectively inducing functional knockout of TRIM46 proteins. Exon 8 inclusion causes nonsense-mediated mRNA decay of Trim46 transcripts. PTBP2-mediated exon 10 skipping produces transcripts encoding unstable TRIM46 proteins. During axonogenesis, transcriptional activation, decreased exon 8 inclusion, and enhanced exon 10 inclusion converge to increase TRIM46 proteins, leading to its neural-specific expression. Genetic deletion of these exons alters TRIM46 protein levels and shows TRIM46 is instructive though not always required for AnkG localization nor a determinant of AnkG density. Therefore, two concurrently but independently regulated alternative exons orchestrate the temporal induction and tissue-specific expression of TRIM46 proteins to mediate axon formation.

Suggested Citation

  • John K. Vuong & Volkan Ergin & Liang Chen & Sika Zheng, 2022. "Multilayered regulations of alternative splicing, NMD, and protein stability control temporal induction and tissue-specific expression of TRIM46 during axon formation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29786-4
    DOI: 10.1038/s41467-022-29786-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29786-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29786-4?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. Hamdan Hamdan & Brian C. Lim & Tomohiro Torii & Abhijeet Joshi & Matthias Konning & Cameron Smith & Donna J. Palmer & Philip Ng & Christophe Leterrier & Juan A. Oses-Prieto & Alma L. Burlingame & Matt, 2020. "Mapping axon initial segment structure and function by multiplexed proximity biotinylation," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    Full references (including those not matched with items on IDEAS)

    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. Wei Zhang & Yu Fu & Luxin Peng & Yuki Ogawa & Xiaoyun Ding & Anne Rasband & Xinyue Zhou & Maya Shelly & Matthew N. Rasband & Peng Zou, 2023. "Immunoproximity biotinylation reveals the axon initial segment proteome," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Yuki Ogawa & Brian C. Lim & Shanu George & Juan A. Oses-Prieto & Joshua M. Rasband & Yael Eshed-Eisenbach & Hamdan Hamdan & Supna Nair & Francesco Boato & Elior Peles & Alma L. Burlingame & Linda Aels, 2023. "Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Chun Chieh Fan & Robert Loughnan & Carolina Makowski & Diliana Pecheva & Chi-Hua Chen & Donald J. Hagler & Wesley K. Thompson & Nadine Parker & Dennis van der Meer & Oleksandr Frei & Ole A. Andreassen, 2022. "Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain," Nature Communications, Nature, vol. 13(1), pages 1-10, 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_s41467-022-29786-4. 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.