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PreprintCited by 10RNA modifications and cancerRNA and protein synthesis mechanismsRNA regulation and disease

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Metabolic turnover and dynamics of modified ribonucleosides by 13 C labeling

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Gameiro, Paulo A., Encheva, Vesela, Dos Santos, Mariana Silva, MacRae, James I, Ule, Jernej·2021·Journal of Biological Chemistry
DOI 10.1101/2021.07.20.453046PMC PMC8567201

Preprint — published as 10.1016/j.jbc.2021.101294 · Paper page

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Abstract

Tandem mass spectrometry (MS/MS) is an accurate tool to assess modified ribonucleosides and their dynamics in mammalian cells. Yet, MS/MS quantification of lowly abundant modifications in non-ribosomal RNAs is unreliable, and the dynamic features of various modifications poorly understood. We developed a 13 C labeling approach, 13 C-dynamods, to quantify the turnover of base modifications in newly transcribed RNA. This turnover-based approach helped to resolve mRNA from ncRNA modifications in purified RNA or free ribonucleosides, and showed the distinct kinetics of N 6-methyladenosine (m 6 2 A) versus 7-methylguanosine (m 7 G) in polyA+-purified RNA. We uncovered that N 6, N 6-dimethyladenosine (m 6 2 A) exhibits a distinct turnover in small RNAs and free ribonucleosides when compared to the known m 6 A-modified large rRNAs. Finally, combined measurements of turnover and abundance informed on the transcriptional versus posttranscriptional sensitivity of modified ncRNAs and mRNAs, respectively, to stress conditions. Thus, 13 C-dynamods enables studies of origin of modified RNAs at steady-state and their dynamics under non-stationary conditions.

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Metadata

Authors
Gameiro, P. A., Encheva, V., Dos Santos, M. S., MacRae, J. I., & Ule, J.
Affiliations
The Francis Crick Institute (GB)
Corresponding author
Gameiro, Paulo A.
ORCID
Venue
Journal of Biological Chemistry
Publisher
openRxiv
Published
2021-07-20
Volume
297
Issue
5
Pages
101294-101294
ISSN
0021-9258 (ISSN-L)
DOI
10.1101/2021.07.20.453046
PMC
PMC8567201
OpenAlex
W3203998404
Cited by
10
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2
FWCI
0.31
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (FP7/2007–2013, FC001002, 103760, 103760/Z/14/, 103760/Z/14/Z)
  • Francis Crick Institute (FC001002, 10011, 10012)
  • Cancer Research UK (FP7/2007-2013, FC001002)
  • European Commission (2007–2013, FP7 2007-2013, FP7/2007, 701730)
  • Seventh Framework Programme (617837)
  • Medical Research Council (FC001002)
  • European Research Council
  • UCL Queen Square Institute of Neurology,University College London (103760/Z/14/Z)
  • H2020 Marie Skłodowska-Curie Actions (701730)
  • FP7 Ideas: European Research Council (617837)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
13C labeling, N6-methyladenosine, 7-methylguanosine, mRNA modification, small RNA, post-transcriptional modification, transcriptional regulation, stress response
MeSH terms
Adenosine, Carbon Isotopes, Guanosine, Isotope Labeling, RNA, RNA Processing, Post-Transcriptional, Tandem Mass Spectrometry

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