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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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