IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49139-7.html
   My bibliography  Save this article

m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation

Author

Listed:
  • Pierre Klein

    (Darwin Building
    The Francis Crick Institute)

  • Marija Petrić Howe

    (The Francis Crick Institute
    University College London)

  • Jasmine Harley

    (The Francis Crick Institute
    University College London)

  • Harry Crook

    (The Francis Crick Institute)

  • Sofia Esteban Serna

    (Darwin Building)

  • Theodoros I. Roumeliotis

    (The Institute of Cancer Research)

  • Jyoti S. Choudhary

    (The Institute of Cancer Research)

  • Anob M. Chakrabarti

    (The Francis Crick Institute)

  • Raphaëlle Luisier

    (Idiap Research Institute
    SIB Swiss Institute of Bioinformatics)

  • Rickie Patani

    (The Francis Crick Institute
    University College London)

  • Andres Ramos

    (Darwin Building)

Abstract

Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.

Suggested Citation

  • Pierre Klein & Marija Petrić Howe & Jasmine Harley & Harry Crook & Sofia Esteban Serna & Theodoros I. Roumeliotis & Jyoti S. Choudhary & Anob M. Chakrabarti & Raphaëlle Luisier & Rickie Patani & Andre, 2024. "m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49139-7
    DOI: 10.1038/s41467-024-49139-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49139-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-49139-7?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. Felicite K. Noubissi & Irina Elcheva & Neehar Bhatia & Abbas Shakoori & Andrei Ougolkov & Jianghuai Liu & Toshinari Minamoto & Jeff Ross & Serge Y. Fuchs & Vladimir S. Spiegelman, 2006. "CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signalling," Nature, Nature, vol. 441(7095), pages 898-901, June.
    2. Dan Dominissini & Sharon Moshitch-Moshkovitz & Schraga Schwartz & Mali Salmon-Divon & Lior Ungar & Sivan Osenberg & Karen Cesarkas & Jasmine Jacob-Hirsch & Ninette Amariglio & Martin Kupiec & Rotem So, 2012. "Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq," Nature, Nature, vol. 485(7397), pages 201-206, May.
    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. Zhen-Dong Zhong & Ying-Yuan Xie & Hong-Xuan Chen & Ye-Lin Lan & Xue-Hong Liu & Jing-Yun Ji & Fu Wu & Lingmei Jin & Jiekai Chen & Daniel W. Mak & Zhang Zhang & Guan-Zheng Luo, 2023. "Systematic comparison of tools used for m6A mapping from nanopore direct RNA sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Zhiyuan Luo & Jiacheng Zhang & Jingyi Fei & Shengdong Ke, 2022. "Deep learning modeling m6A deposition reveals the importance of downstream cis-element sequences," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Fernando Rodriguez & Irina A. Yushenova & Daniel DiCorpo & Irina R. Arkhipova, 2022. "Bacterial N4-methylcytosine as an epigenetic mark in eukaryotic DNA," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Harini Ramalingam & Jesus Alvarez & Andrea Flaten & Patricia Cobo-Stark & Nicholas Foster & Elyse Grilli & Ronak Lakhia & Karam Aboudehen & Thomas Carroll & Vishal Patel, 2025. "An RNA transmethylation pathway governs kidney nephrogenic potential," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    5. Shreya Rajachandran & Qianlan Xu & Qiqi Cao & Xin Zhang & Fei Chen & Sarah M. Mangiameli & Haiqi Chen, 2025. "Subcellular level spatial transcriptomics with PHOTON," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    6. Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Guoqiang Zhang & Yongru Xu & Xiaona Wang & Yuanxiang Zhu & Liangliang Wang & Wenxin Zhang & Yiru Wang & Yajie Gao & Xuna Wu & Ying Cheng & Qinmiao Sun & Dahua Chen, 2022. "Dynamic FMR1 granule phase switch instructed by m6A modification contributes to maternal RNA decay," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. P Acera Mateos & A J Sethi & A Ravindran & A Srivastava & K Woodward & S Mahmud & M Kanchi & M Guarnacci & J Xu & Z W S Yuen & Y Zhou & A Sneddon & W Hamilton & J Gao & L M Starrs & R Hayashi & V Wick, 2024. "Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Zhijun Ren & Jialiang He & Xiang Huang & Yan Gao & Chuanchuan Wei & Zehong Wu & Wenbing Guo & Feng Wang & Qingquan Zhao & Xiang Sun & Jie Zhang & Nan Cao & Lan Lin & Jinkai Wang & Yixian Cun, 2025. "Isoform characterization of m6A in single cells identifies its role in RNA surveillance," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    10. Zhenxing Guo & Daoyu Duan & Wen Tang & Julia Zhu & William S Bush & Liangliang Zhang & Xiaofeng Zhu & Fulai Jin & Hao Feng, 2024. "magpie: A power evaluation method for differential RNA methylation analysis in N6-methyladenosine sequencing," PLOS Computational Biology, Public Library of Science, vol. 20(2), pages 1-13, February.
    11. Xiangyu Wang & Yan Ding & Ran Li & Rujun Zhang & Xuejun Ge & Ruifang Gao & Miao Wang & Yubing Huang & Fang Zhang & Bin Zhao & Wang Liao & Jie Du, 2023. "N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Qiang Luo & Jiezhen Mo & Hao Chen & Zetao Hu & Baihui Wang & Jiabing Wu & Ziyu Liang & Wenhao Xie & Kangxi Du & Maolin Peng & Yingping Li & Tianyang Li & Yangyi Zhang & Xiaoyan Shi & Wen-Hui Shen & Ya, 2022. "Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. 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.
    14. 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.
    15. You Wu & Wenna Shao & Mengxiao Yan & Yuqin Wang & Pengfei Xu & Guoqiang Huang & Xiaofei Li & Brian D. Gregory & Jun Yang & Hongxia Wang & Xiang Yu, 2024. "Transfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    16. Song-Yao Zhang & Shao-Wu Zhang & Lian Liu & Jia Meng & Yufei Huang, 2016. "m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks," PLOS Computational Biology, Public Library of Science, vol. 12(12), pages 1-31, December.
    17. Adrien Leger & Paulo P. Amaral & Luca Pandolfini & Charlotte Capitanchik & Federica Capraro & Valentina Miano & Valentina Migliori & Patrick Toolan-Kerr & Theodora Sideri & Anton J. Enright & Konstant, 2021. "RNA modifications detection by comparative Nanopore direct RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    18. Hyun Jung Hwang & Tae Lim Park & Hyeong-In Kim & Yeonkyoung Park & Geunhee Kim & Chiyeol Song & Won-Ki Cho & Yoon Ki Kim, 2023. "YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Moshe Shay Ben-Haim & Yishay Pinto & Sharon Moshitch-Moshkovitz & Vera Hershkovitz & Nitzan Kol & Tammy Diamant-Levi & Michal Schnaider Beeri & Ninette Amariglio & Haim Y. Cohen & Gideon Rechavi, 2021. "Dynamic regulation of N6,2′-O-dimethyladenosine (m6Am) in obesity," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    20. Dongsheng Mao & Xiaochen Tang & Runchi Zhang & Song Hu & Hongquan Gou & Penghui Zhang & Wenxing Li & Qiuhui Pan & Bing Shen & Xiaoli Zhu, 2025. "Multichrome encoding-based multiplexed, spatially resolved imaging reveals single-cell RNA epigenetic modifications heterogeneity," Nature Communications, Nature, vol. 16(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_s41467-024-49139-7. 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.