IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46943-z.html
   My bibliography  Save this article

A rapid inducible RNA decay system reveals fast mRNA decay in P-bodies

Author

Listed:
  • Lauren A. Blake

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

  • Leslie Watkins

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

  • Yang Liu

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

  • Takanari Inoue

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

  • Bin Wu

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

Abstract

RNA decay is vital for regulating mRNA abundance and gene expression. Existing technologies lack the spatiotemporal precision or transcript specificity to capture the stochastic and transient decay process. We devise a general strategy to inducibly recruit protein factors to modulate target RNA metabolism. Specifically, we introduce a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNAs within minutes. The fast and synchronous induction enables direct visualization of mRNA decay dynamics in cells. Applying RIDR to endogenous ACTB mRNA reveals rapid formation and dissolution of RNA granules in pre-existing P-bodies. Time-resolved RNA distribution measurements demonstrate rapid RNA decay inside P-bodies, which is further supported by knocking down P-body constituent proteins. Light and oxidative stress modulate P-body behavior, potentially reconciling the contradictory literature about P-body function. This study reveals compartmentalized RNA decay kinetics, establishing RIDR as a pivotal tool for exploring the spatiotemporal RNA metabolism in cells.

Suggested Citation

  • Lauren A. Blake & Leslie Watkins & Yang Liu & Takanari Inoue & Bin Wu, 2024. "A rapid inducible RNA decay system reveals fast mRNA decay in P-bodies," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46943-z
    DOI: 10.1038/s41467-024-46943-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46943-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-46943-z?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. Yi Fu & Pedro P. Rocha & Vincent M. Luo & Ramya Raviram & Yan Deng & Esteban O. Mazzoni & Jane A. Skok, 2016. "CRISPR-dCas9 and sgRNA scaffolds enable dual-colour live imaging of satellite sequences and repeat-enriched individual loci," Nature Communications, Nature, vol. 7(1), pages 1-8, September.
    2. 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.
    3. Peiwu Qin & Mahmut Parlak & Cem Kuscu & Jigar Bandaria & Mustafa Mir & Karol Szlachta & Ritambhara Singh & Xavier Darzacq & Ahmet Yildiz & Mazhar Adli, 2017. "Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    4. Shaopeng Wang & Malgorzata J. Latallo & Zhe Zhang & Bo Huang & Dmitriy G. Bobrovnikov & Daoyuan Dong & Nathan M. Livingston & Wilson Tjoeng & Lindsey R. Hayes & Jeffrey D. Rothstein & Lyle W. Ostrow &, 2021. "Nuclear export and translation of circular repeat-containing intronic RNA in C9ORF72-ALS/FTD," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    5. Omar O. Abudayyeh & Jonathan S. Gootenberg & Patrick Essletzbichler & Shuo Han & Julia Joung & Joseph J. Belanto & Vanessa Verdine & David B. T. Cox & Max J. Kellner & Aviv Regev & Eric S. Lander & Da, 2017. "RNA targeting with CRISPR–Cas13," Nature, Nature, vol. 550(7675), pages 280-284, October.
    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. 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. 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.
    3. 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.
    4. Feiyu Zhao & Tao Zhang & Xiaodi Sun & Xiyun Zhang & Letong Chen & Hejun Wang & Jinze Li & Peng Fan & Liangxue Lai & Tingting Sui & Zhanjun Li, 2023. "A strategy for Cas13 miniaturization based on the structure and AlphaFold," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. David N. Fiflis & Nicolas A. Rey & Harshitha Venugopal-Lavanya & Beatrice Sewell & Aaron Mitchell-Dick & Katie N. Clements & Sydney Milo & Abigail R. Benkert & Alan Rosales & Sophia Fergione & Aravind, 2024. "Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Pei Liu & Josquin Foiret & Yinglin Situ & Nisi Zhang & Aris J. Kare & Bo Wu & Marina N. Raie & Katherine W. Ferrara & Lei S. Qi, 2023. "Sonogenetic control of multiplexed genome regulation and base editing," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Hongrui Zhao & Yan Sheng & Tenghua Zhang & Shujun Zhou & Yuqing Zhu & Feiyang Qian & Meiru Liu & Weixue Xu & Dengsong Zhang & Jiaming Hu, 2024. "The CRISPR-Cas13a Gemini System for noncontiguous target RNA activation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Zhifang Li & Ruochen Guo & Xiaozhi Sun & Guoling Li & Zhuang Shao & Xiaona Huo & Rongrong Yang & Xinyu Liu & Xi Cao & Hainan Zhang & Weihong Zhang & Xiaoyin Zhang & Shuangyu Ma & Meiling Zhang & Yuanh, 2024. "Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    9. Patricia A. Clow & Menghan Du & Nathaniel Jillette & Aziz Taghbalout & Jacqueline J. Zhu & Albert W. Cheng, 2022. "CRISPR-mediated multiplexed live cell imaging of nonrepetitive genomic loci with one guide RNA per locus," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    10. Evan A. Schwartz & Jack P. K. Bravo & Mohd Ahsan & Luis A. Macias & Caitlyn L. McCafferty & Tyler L. Dangerfield & Jada N. Walker & Jennifer S. Brodbelt & Giulia Palermo & Peter C. Fineran & Robert D., 2024. "RNA targeting and cleavage by the type III-Dv CRISPR effector complex," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. M. Alejandra Zeballos C. & Hayden J. Moore & Tyler J. Smith & Jackson E. Powell & Najah S. Ahsan & Sijia Zhang & Thomas Gaj, 2023. "Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Yage Ding & Cristina Tous & Jaehoon Choi & Jingyao Chen & Wilson W. Wong, 2024. "Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    13. Jeonghye Yu & Jongpil Shin & Jihwan Yu & Jihye Kim & Daseuli Yu & Won Do Heo, 2024. "Programmable RNA base editing with photoactivatable CRISPR-Cas13," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    14. Zhongxuan Zhang & Xiaoxiao Rong & Tianjin Xie & Zehao Li & Haozhi Song & Shujun Zhen & Haifeng Wang & Jiahui Wu & Samie R. Jaffrey & Xing Li, 2024. "Fluorogenic CRISPR for genomic DNA imaging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    15. Xiangyu Deng & Emmanuel Osikpa & Jie Yang & Seye J. Oladeji & Jamie Smith & Xue Gao & Yang Gao, 2023. "Structural basis for the activation of a compact CRISPR-Cas13 nuclease," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    16. Jianli Tao & Daniel E. Bauer & Roberto Chiarle, 2023. "Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    17. Xiaolong Cheng & Zexu Li & Ruocheng Shan & Zihan Li & Shengnan Wang & Wenchang Zhao & Han Zhang & Lumen Chao & Jian Peng & Teng Fei & Wei Li, 2023. "Modeling CRISPR-Cas13d on-target and off-target effects using machine learning approaches," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Yanan Li & Yonghua Wu & Ru Xu & Jialing Guo & Fenglei Quan & Yongyuan Zhang & Di Huang & Yiran Pei & Hua Gao & Wei Liu & Junjie Liu & Zhenzhong Zhang & Ruijie Deng & Jinjin Shi & Kaixiang Zhang, 2023. "In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Duško Lainšček & Vida Forstnerič & Veronika Mikolič & Špela Malenšek & Peter Pečan & Mojca Benčina & Matjaž Sever & Helena Podgornik & Roman Jerala, 2022. "Coiled-coil heterodimer-based recruitment of an exonuclease to CRISPR/Cas for enhanced gene editing," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Ryan P. Hildebrandt & Kathryn R. Moss & Aleksandra Janusz-Kaminska & Luke A. Knudson & Lance T. Denes & Tanvi Saxena & Devi Prasad Boggupalli & Zhuangyue Li & Kun Lin & Gary J. Bassell & Eric T. Wang, 2023. "Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes," Nature Communications, Nature, vol. 14(1), pages 1-19, 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_s41467-024-46943-z. 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.