IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51284-y.html
   My bibliography  Save this article

OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress

Author

Listed:
  • Sammy Villa

    (University of California
    1170 Veterans Boulevard)

  • Pankaj Dwivedi

    (1 DNA Way
    Merck)

  • Aaron Stahl

    (University of Iowa
    Scripps Research)

  • Trent Hinkle

    (1 DNA Way)

  • Christopher M. Rose

    (1 DNA Way)

  • Donald S. Kirkpatrick

    (1 DNA Way
    Xaira Therapeutics)

  • Seth M. Tomchik

    (University of Iowa
    Scripps Research
    University of Iowa
    University of Iowa)

  • Vishva M. Dixit

    (1 DNA Way)

  • Fred W. Wolf

    (University of California
    University of California)

Abstract

Ribosomes are regulated by evolutionarily conserved ubiquitination/deubiquitination events. We uncover the role of the deubiquitinase OTUD6 in regulating global protein translation through deubiquitination of the RPS7/eS7 subunit on the free 40 S ribosome in vivo in Drosophila. Coimmunoprecipitation and enrichment of monoubiquitinated proteins from catalytically inactive OTUD6 flies reveal RPS7 as the ribosomal substrate. The 40 S protein RACK1 and E3 ligases CNOT4 and RNF10 function upstream of OTUD6 to regulate alkylation stress. OTUD6 interacts with RPS7 specifically on the free 40 S, and not on 43 S/48 S initiation complexes or the translating ribosome. Global protein translation levels are bidirectionally regulated by OTUD6 protein abundance. OTUD6 protein abundance is physiologically regulated in aging and in response to translational and alkylation stress. Thus, OTUD6 may promote translation initiation, the rate limiting step in protein translation, by titering the amount of 40 S ribosome that recycles.

Suggested Citation

  • Sammy Villa & Pankaj Dwivedi & Aaron Stahl & Trent Hinkle & Christopher M. Rose & Donald S. Kirkpatrick & Seth M. Tomchik & Vishva M. Dixit & Fred W. Wolf, 2024. "OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51284-y
    DOI: 10.1038/s41467-024-51284-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51284-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51284-y?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. Anna B. Loveland & Egor Svidritskiy & Denis Susorov & Soojin Lee & Alexander Park & Sarah Zvornicanin & Gabriel Demo & Fen-Biao Gao & Andrei A. Korostelev, 2022. "Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Yoshitaka Matsuo & Ken Ikeuchi & Yasushi Saeki & Shintaro Iwasaki & Christian Schmidt & Tsuyoshi Udagawa & Fumiya Sato & Hikaru Tsuchiya & Thomas Becker & Keiji Tanaka & Nicholas T. Ingolia & Roland B, 2017. "Ubiquitination of stalled ribosome triggers ribosome-associated quality control," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Liewei L. Yan & Carrie L. Simms & Fionn McLoughlin & Richard D. Vierstra & Hani S. Zaher, 2019. "Oxidation and alkylation stresses activate ribosome-quality control," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Ken Ikeuchi & Nives Ivic & Robert Buschauer & Jingdong Cheng & Thomas Fröhlich & Yoshitaka Matsuo & Otto Berninghausen & Toshifumi Inada & Thomas Becker & Roland Beckmann, 2023. "Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Susan E. Celniker & Laura A. L. Dillon & Mark B. Gerstein & Kristin C. Gunsalus & Steven Henikoff & Gary H. Karpen & Manolis Kellis & Eric C. Lai & Jason D. Lieb & David M. MacAlpine & Gos Micklem & F, 2009. "Unlocking the secrets of the genome," Nature, Nature, vol. 459(7249), pages 927-930, June.
    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. Malgorzata J. Latallo & Shaopeng Wang & Daoyuan Dong & Blake Nelson & Nathan M. Livingston & Rong Wu & Ning Zhao & Timothy J. Stasevich & Michael C. Bassik & Shuying Sun & Bin Wu, 2023. "Single-molecule imaging reveals distinct elongation and frameshifting dynamics between frames of expanded RNA repeats in C9ORF72-ALS/FTD," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Yoshitaka Matsuo & Takayuki Uchihashi & Toshifumi Inada, 2023. "Decoding of the ubiquitin code for clearance of colliding ribosomes by the RQT complex," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Phillip C. Burke & Heungwon Park & Arvind Rasi Subramaniam, 2022. "A nascent peptide code for translational control of mRNA stability in human cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Antonios Apostolopoulos & Naohiro Kawamoto & Siu Yu A. Chow & Hitomi Tsuiji & Yoshiho Ikeuchi & Yuichi Shichino & Shintaro Iwasaki, 2024. "dCas13-mediated translational repression for accurate gene silencing in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Xinhao Hou & Mingjing Xu & Chengming Zhu & Jianing Gao & Meili Li & Xiangyang Chen & Cheng Sun & Björn Nashan & Jianye Zang & Ying Zhou & Shouhong Guang & Xuezhu Feng, 2023. "Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Yayoi Natsume-Kitatani & Hiroshi Mamitsuka, 2016. "Classification of Promoters Based on the Combination of Core Promoter Elements Exhibits Different Histone Modification Patterns," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-18, March.
    7. Pavel V. Panteleev & Eugene B. Pichkur & Roman N. Kruglikov & Alena Paleskava & Olga V. Shulenina & Ilia A. Bolosov & Ivan V. Bogdanov & Victoria N. Safronova & Sergey V. Balandin & Valeriya I. Marina, 2024. "Rumicidins are a family of mammalian host-defense peptides plugging the 70S ribosome exit tunnel," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    9. Ken Ikeuchi & Nives Ivic & Robert Buschauer & Jingdong Cheng & Thomas Fröhlich & Yoshitaka Matsuo & Otto Berninghausen & Toshifumi Inada & Thomas Becker & Roland Beckmann, 2023. "Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Dahong Chen & Catherine E. McManus & Behram Radmanesh & Leah H. Matzat & Elissa P. Lei, 2021. "Temporal inhibition of chromatin looping and enhancer accessibility during neuronal remodeling," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    11. Momoko Narita & Timo Denk & Yoshitaka Matsuo & Takato Sugiyama & Chisato Kikuguchi & Sota Ito & Nichika Sato & Toru Suzuki & Satoshi Hashimoto & Iva Machová & Petr Tesina & Roland Beckmann & Toshifumi, 2022. "A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Shijia Zhu & Guohua Wang & Bo Liu & Yadong Wang, 2013. "Modeling Exon Expression Using Histone Modifications," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-15, June.
    13. Katharina Best & Ken Ikeuchi & Lukas Kater & Daniel Best & Joanna Musial & Yoshitaka Matsuo & Otto Berninghausen & Thomas Becker & Toshifumi Inada & Roland Beckmann, 2023. "Structural basis for clearing of ribosome collisions by the RQT complex," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    14. Junqiao Jia & Tarek Hilal & Katherine E. Bohnsack & Aleksandar Chernev & Ning Tsao & Juliane Bethmann & Aruna Arumugam & Lane Parmely & Nicole Holton & Bernhard Loll & Nima Mosammaparast & Markus T. B, 2023. "Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Yudong Fu & Fan Jiang & Xiao Zhang & Yingyi Pan & Rui Xu & Xiu Liang & Xiaofen Wu & Xingqiang Li & Kaixuan Lin & Ruona Shi & Xiaofei Zhang & Dominique Ferrandon & Jing Liu & Duanqing Pei & Jie Wang & , 2024. "Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    16. Jingting Xu & Hong Hu & Yang Dai, 2016. "LMethyR-SVM: Predict Human Enhancers Using Low Methylated Regions based on Weighted Support Vector Machines," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-18, September.
    17. Hao Wu & Hongkai Ji, 2014. "PolyaPeak: Detecting Transcription Factor Binding Sites from ChIP-seq Using Peak Shape Information," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-9, March.
    18. Jiangnan Liu & Noemi Nagy & Carlos Ayala-Torres & Francisco Aguilar-Alonso & Francisco Morais-Esteves & Shanshan Xu & Maria G. Masucci, 2023. "Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Ji Geng & Shuangxi Li & Yu Li & Zhihao Wu & Sunil Bhurtel & Suman Rimal & Danish Khan & Rani Ohja & Onn Brandman & Bingwei Lu, 2024. "Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Yosuke Ito & Yuhei Chadani & Tatsuya Niwa & Ayako Yamakawa & Kodai Machida & Hiroaki Imataka & Hideki Taguchi, 2022. "Nascent peptide-induced translation discontinuation in eukaryotes impacts biased amino acid usage in proteomes," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:15:y:2024:i:1:d:10.1038_s41467-024-51284-y. 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.