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The extensive m5C epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily

Author

Listed:
  • Kristin A. Fluke

    (Colorado State University)

  • Ryan T. Fuchs

    (New England Biolabs Inc.)

  • Yueh-Lin Tsai

    (New England Biolabs Inc.)

  • Victoria Talbott

    (Colorado State University)

  • Liam Elkins

    (Colorado State University)

  • Hallie P. Febvre

    (Colorado State University)

  • Nan Dai

    (New England Biolabs Inc.)

  • Eric J. Wolf

    (New England Biolabs Inc.)

  • Brett W. Burkhart

    (Colorado State University)

  • Jackson Schiltz

    (Colorado State University)

  • G. Brett Robb

    (New England Biolabs Inc.)

  • Ivan R. Corrêa

    (New England Biolabs Inc.)

  • Thomas J. Santangelo

    (Colorado State University
    Colorado State University)

Abstract

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (m5C) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of m5C have yet to be fully investigated. Here, we map m5C in the model hyperthermophile, Thermococcus kodakarensis. We demonstrate that m5C is ~25x more abundant in T. kodakarensis than human cells, and the m5C epitranscriptome includes ~10% of unique transcripts. T. kodakarensis rRNAs harbor tenfold more m5C compared to Eukarya or Bacteria. We identify at least five RNA m5C methyltransferases (R5CMTs), and strains deleted for individual R5CMTs lack site-specific m5C modifications that limit hyperthermophilic growth. We show that m5C is likely generated through partial redundancy in target sites among R5CMTs. The complexity of the m5C epitranscriptome in T. kodakarensis argues that m5C supports life in the extremes.

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  • Kristin A. Fluke & Ryan T. Fuchs & Yueh-Lin Tsai & Victoria Talbott & Liam Elkins & Hallie P. Febvre & Nan Dai & Eric J. Wolf & Brett W. Burkhart & Jackson Schiltz & G. Brett Robb & Ivan R. Corrêa & T, 2024. "The extensive m5C epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51410-w
    DOI: 10.1038/s41467-024-51410-w
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    1. Nian Liu & Qing Dai & Guanqun Zheng & Chuan He & Marc Parisien & Tao Pan, 2015. "N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions," Nature, Nature, vol. 518(7540), pages 560-564, February.
    2. Hao Du & Ya Zhao & Jinqiu He & Yao Zhang & Hairui Xi & Mofang Liu & Jinbiao Ma & Ligang Wu, 2016. "YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    3. Aldema Sas-Chen & Justin M. Thomas & Donna Matzov & Masato Taoka & Kellie D. Nance & Ronit Nir & Keri M. Bryson & Ran Shachar & Geraldy L. S. Liman & Brett W. Burkhart & Supuni Thalalla Gamage & Yuko , 2020. "Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping," Nature, Nature, vol. 583(7817), pages 638-643, July.
    4. Sandra Blanco & Roberto Bandiera & Martyna Popis & Shobbir Hussain & Patrick Lombard & Jelena Aleksic & Abdulrahim Sajini & Hinal Tanna & Rosana Cortés-Garrido & Nikoletta Gkatza & Sabine Dietmann & M, 2016. "Stem cell function and stress response are controlled by protein synthesis," Nature, Nature, vol. 534(7607), pages 335-340, June.
    5. Qicong Shen & Qian Zhang & Yang Shi & Qingzhu Shi & Yanyan Jiang & Yan Gu & Zhiqing Li & Xia Li & Kai Zhao & Chunmei Wang & Nan Li & Xuetao Cao, 2018. "Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation," Nature, Nature, vol. 554(7690), pages 123-127, February.
    6. Xiao Wang & Zhike Lu & Adrian Gomez & Gary C. Hon & Yanan Yue & Dali Han & Ye Fu & Marc Parisien & Qing Dai & Guifang Jia & Bing Ren & Tao Pan & Chuan He, 2014. "N6-methyladenosine-dependent regulation of messenger RNA stability," Nature, Nature, vol. 505(7481), pages 117-120, January.
    7. Takayuki Ohira & Keiichi Minowa & Kei Sugiyama & Seisuke Yamashita & Yuriko Sakaguchi & Kenjyo Miyauchi & Ryo Noguchi & Akira Kaneko & Izumi Orita & Toshiaki Fukui & Kozo Tomita & Tsutomu Suzuki, 2022. "Reversible RNA phosphorylation stabilizes tRNA for cellular thermotolerance," Nature, Nature, vol. 605(7909), pages 372-379, May.
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