IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29790-8.html
   My bibliography  Save this article

TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer

Author

Listed:
  • Zhangli Su

    (University of Alabama
    University of Virginia)

  • Ida Monshaugen

    (Oslo University Hospital Rikshospitalet
    University of Oslo
    Baerum Hospital Vestre Viken Hospital Trust)

  • Briana Wilson

    (University of Virginia)

  • Fengbin Wang

    (University of Virginia)

  • Arne Klungland

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Rune Ougland

    (Oslo University Hospital Rikshospitalet
    Baerum Hospital Vestre Viken Hospital Trust)

  • Anindya Dutta

    (University of Alabama
    University of Virginia)

Abstract

RNA modifications are important regulatory elements of RNA functions. However, most genome-wide mapping of RNA modifications has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N1-methyladenosine (m1A) in the cellular small RNA space. Benchmarked with synthetic m1A RNAs, our workflow identified specific groups of m1A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3′ tRNA-fragments are highly enriched for TRMT6/61A-dependent m1A located within the seed region. TRMT6/61A-dependent m1A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m1A modification on tRFs is detected, correlated with a dysregulation of tRF targetome. Lastly, TRMT6/61A regulates tRF-3 targets involved in unfolded protein response. Together, our results reveal a mechanism of regulating gene expression via base modification of small RNA.

Suggested Citation

  • Zhangli Su & Ida Monshaugen & Briana Wilson & Fengbin Wang & Arne Klungland & Rune Ougland & Anindya Dutta, 2022. "TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29790-8
    DOI: 10.1038/s41467-022-29790-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29790-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-29790-8?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. Ryan J. Golden & Beibei Chen & Tuo Li & Juliane Braun & Hema Manjunath & Xiang Chen & Jiaxi Wu & Vanessa Schmid & Tsung-Cheng Chang & Florian Kopp & Andres Ramirez-Martinez & Vincent S. Tagliabracci &, 2017. "An Argonaute phosphorylation cycle promotes microRNA-mediated silencing," Nature, Nature, vol. 542(7640), pages 197-202, February.
    2. Emily M. Harcourt & Anna M. Kietrys & Eric T. Kool, 2017. "Chemical and structural effects of base modifications in messenger RNA," Nature, Nature, vol. 541(7637), pages 339-346, January.
    3. Anya V. Grozhik & Anthony O. Olarerin-George & Miriam Sindelar & Xing Li & Steven S. Gross & Samie R. Jaffrey, 2019. "Antibody cross-reactivity accounts for widespread appearance of m1A in 5’UTRs," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    4. Hak Kyun Kim & Gabriele Fuchs & Shengchun Wang & Wei Wei & Yue Zhang & Hyesuk Park & Biswajoy Roy-Chaudhuri & Pan Li & Jianpeng Xu & Kirk Chu & Feijie Zhang & Mei-Sze Chua & Samuel So & Qiangfeng Clif, 2017. "A transfer-RNA-derived small RNA regulates ribosome biogenesis," Nature, Nature, vol. 552(7683), pages 57-62, December.
    5. Michael H. Schwartz & Haipeng Wang & Jessica N. Pan & Wesley C. Clark & Steven Cui & Matthew J. Eckwahl & David W. Pan & Marc Parisien & Sarah M. Owens & Brian L. Cheng & Kristina Martinez & Jinbo Xu , 2018. "Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Dan Dominissini & Sigrid Nachtergaele & Sharon Moshitch-Moshkovitz & Eyal Peer & Nitzan Kol & Moshe Shay Ben-Haim & Qing Dai & Ayelet Di Segni & Mali Salmon-Divon & Wesley C. Clark & Guanqun Zheng & T, 2016. "The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA," Nature, Nature, vol. 530(7591), pages 441-446, February.
    7. Takeo Suzuki & Yuka Yashiro & Ittoku Kikuchi & Yuma Ishigami & Hironori Saito & Ikuya Matsuzawa & Shunpei Okada & Mari Mito & Shintaro Iwasaki & Ding Ma & Xuewei Zhao & Kana Asano & Huan Lin & Yohei K, 2020. "Complete chemical structures of human mitochondrial tRNAs," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    8. Modi Safra & Aldema Sas-Chen & Ronit Nir & Roni Winkler & Aharon Nachshon & Dan Bar-Yaacov & Matthias Erlacher & Walter Rossmanith & Noam Stern-Ginossar & Schraga Schwartz, 2017. "The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution," Nature, Nature, vol. 551(7679), pages 251-255, November.
    9. Kizzmekia S. Corbett & Darin K. Edwards & Sarah R. Leist & Olubukola M. Abiona & Seyhan Boyoglu-Barnum & Rebecca A. Gillespie & Sunny Himansu & Alexandra Schäfer & Cynthia T. Ziwawo & Anthony T. DiPia, 2020. "SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness," Nature, Nature, vol. 586(7830), pages 567-571, October.
    10. Konstantin Khetchoumian & Aurélio Balsalobre & Alexandre Mayran & Helen Christian & Valérie Chénard & Julie St-Pierre & Jacques Drouin, 2019. "Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    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. Hongna Zuo & Aiwei Wu & Mingwei Wang & Liquan Hong & Hu Wang, 2024. "tRNA m1A modification regulate HSC maintenance and self-renewal via mTORC1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-13, 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. Belinda Baquero-Pérez & Ivaylo D. Yonchev & Anna Delgado-Tejedor & Rebeca Medina & Mireia Puig-Torrents & Ian Sudbery & Oguzhan Begik & Stuart A. Wilson & Eva Maria Novoa & Juana Díez, 2024. "N6-methyladenosine modification is not a general trait of viral RNA genomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Katja Hartstock & Nadine A. Kueck & Petr Spacek & Anna Ovcharenko & Sabine Hüwel & Nicolas V. Cornelissen & Amarnath Bollu & Christoph Dieterich & Andrea Rentmeister, 2023. "MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Hongna Zuo & Aiwei Wu & Mingwei Wang & Liquan Hong & Hu Wang, 2024. "tRNA m1A modification regulate HSC maintenance and self-renewal via mTORC1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Neeltje van Doremalen & Jonathan E. Schulz & Danielle R. Adney & Taylor A. Saturday & Robert J. Fischer & Claude Kwe Yinda & Nazia Thakur & Joseph Newman & Marta Ulaszewska & Sandra Belij-Rammerstorfe, 2022. "ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Christopher P. Watkins & Wen Zhang & Adam C. Wylder & Christopher D. Katanski & Tao Pan, 2022. "A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Yanying Wang & Jing Wang & Xiaoyu Li & Xushen Xiong & Jianyi Wang & Ziheng Zhou & Xiaoxiao Zhu & Yang Gu & Dan Dominissini & Lei He & Yong Tian & Chengqi Yi & Zusen Fan, 2021. "N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    7. Wenjun Zhu & Ting Wei & Yuchun Xu & Qiutong Jin & Yu Chao & Jiaqi Lu & Jun Xu & Jiafei Zhu & Xiaoying Yan & Muchao Chen & Qian Chen & Zhuang Liu, 2024. "Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Vincent Meynier & Steven W. Hardwick & Marjorie Catala & Johann J. Roske & Stephanie Oerum & Dimitri Y. Chirgadze & Pierre Barraud & Wyatt W. Yue & Ben F. Luisi & Carine Tisné, 2024. "Structural basis for human mitochondrial tRNA maturation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Paula Clemente & Javier Calvo-Garrido & Sarah F. Pearce & Florian A. Schober & Megumi Shigematsu & Stefan J. Siira & Isabelle Laine & Henrik Spåhr & Christian Steinmetzger & Katja Petzold & Yohei Kiri, 2022. "ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Hejin Lai & Ning Feng & Qiwei Zhai, 2023. "Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Carlos Ávila-Nieto & Júlia Vergara-Alert & Pep Amengual-Rigo & Erola Ainsua-Enrich & Marco Brustolin & María Luisa Rodríguez de la Concepción & Núria Pedreño-Lopez & Jordi Rodon & Victor Urrea & Edwar, 2024. "Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Tian-Yu Song & Min Long & Hai-Xin Zhao & Miao-Wen Zou & Hong-Jie Fan & Yang Liu & Chen-Lu Geng & Min-Fang Song & Yu-Feng Liu & Jun-Yi Chen & Yu-Lin Yang & Wen-Rong Zhou & Da-Wei Huang & Bo Peng & Zhen, 2021. "Tumor evolution selectively inactivates the core microRNA machinery for immune evasion," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    13. Seongryong Kim & Ji Hyang Jeon & Myeonghwan Kim & Yeji Lee & Yun-Ho Hwang & Myungsun Park & C. Han Li & Taeyoung Lee & Jung-Ah Lee & You-Me Kim & Dokeun Kim & Hyukjin Lee & You-Jin Kim & V. Narry Kim , 2024. "Innate immune responses against mRNA vaccine promote cellular immunity through IFN-β at the injection site," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    15. Tingting Niu & Charlotte Rosny & Séverine Chautard & Amaury Rey & Danish Patoli & Marine Groslambert & Camille Cosson & Brice Lagrange & Zhirong Zhang & Orane Visvikis & Sabine Hacot & Maggy Hologne &, 2021. "NLRP3 phosphorylation in its LRR domain critically regulates inflammasome assembly," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    16. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Ainara González-Iglesias & Aida Arcas & Ana Domingo-Muelas & Estefania Mancini & Joan Galcerán & Juan Valcárcel & Isabel Fariñas & M. Angela Nieto, 2024. "Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    18. Kathrin Leppek & Gun Woo Byeon & Wipapat Kladwang & Hannah K. Wayment-Steele & Craig H. Kerr & Adele F. Xu & Do Soon Kim & Ved V. Topkar & Christian Choe & Daphna Rothschild & Gerald C. Tiu & Roger We, 2022. "Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    19. Charlotte A. Cialek & Gabriel Galindo & Tatsuya Morisaki & Ning Zhao & Taiowa A. Montgomery & Timothy J. Stasevich, 2022. "Imaging translational control by Argonaute with single-molecule resolution in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Vivek Singh & Yuzuru Itoh & Samuel Del’Olio & Asem Hassan & Andreas Naschberger & Rasmus Kock Flygaard & Yuko Nobe & Keiichi Izumikawa & Shintaro Aibara & Juni Andréll & Paul C. Whitford & Antoni Barr, 2024. "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk," Nature Communications, Nature, vol. 15(1), pages 1-22, 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_s41467-022-29790-8. 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.