Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 35 min ago
Peer-reviewedCC BYCell

Functional diversification of the cephalopod proteome by RNA-editing

  • Jack M. Moen1,2,3
  • Alicia L. Richards1,2,3
  • Einar K. Krogsaeter1,2,3
  • Benjamin J. Polacco1,2,3
  • Martin Gordon1,2,3
  • Erica Stevenson1,2,3
  • Rhiana Boyles4
  • Maximilien Burq5
  • Dejan Stepec5
  • Bryan Crampton5
  • Nathaniel Sin6,7
  • Zachary Gale-Day6,7
5 more authors
  • Jason E. Gestwicki6,7
  • Peter Cimermancic5
  • Joshua J. C. Rosenthal4
  • Nevan J. Krogan1,2,3
  • Danielle L. Swaney1,2,3,8
8 affiliations
  1. 1Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, California, 94143, USA
  2. 2Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, 94143, USA
  3. 3Data Science and Biotechnology Institute, J. David Gladstone Institutes, San Francisco, California, 94158, USA
  4. 4The Eugene Bell Center, The Marine Biological Laboratory, Woods Hole, Massachusetts, 02543, USA
  5. 5Tesorai Inc., 3525 Del Mar Heights Rd, 284, San Diego, California, 92130 USA
  6. 6Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA
  7. 7Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, 94158, USA
  8. 8Lead contact
Read full textDOICite

Abstract

Coleoid cephalopods exhibit the highest levels of adenosine deaminases acting on RNA (ADAR)-mediated RNA editing of any known taxon, yet the functional consequences of most recoding events remain unclear. Here, we integrated proteomics with biochemical and cellular assays to characterize recoding across the Doryteuthis pealeii proteome. This confirmed the translation of 7,997 recoded sites at the protein level and revealed how recoding reshapes the proteome by altering protein stability, subcellular localization, post-translational modifications, and enzymatic activity. We find that recoding also creates or ablates post-translational modification sites, with direct effects on protein function and protein-protein interactions. Recoding the E3 ligase MARCHF5 drives widespread changes in substrate ubiquitylation and perturbs mitochondrial homeostasis, illustrating how RNA editing can influence organelle function. Together, these data give a proteome-scale view of how extensive RNA recoding diversifies protein function in coleoid cephalopods and offer a framework for understanding how RNA-level plasticity shapes protein function and cellular physiology.

Related

  1. Functional diversification of CsCAD14 orchestrates synergistic phenylpropanoid biosynthesis to defend gray blight disease in tea plants
    Linlin Xu, Songyan Huang, Jie Deng +10
    Science AdvancesPeer-reviewedCC BY-NCMolecular biology & gene regulationCrossref
  2. A functional map of the human intrinsically disordered proteome
    Iva Pritišanac, T. Reid Alderson, Đesika Kolarić +8
    Proceedings of the National Academy of SciencesPeer-reviewedCC BY-NC-ND38 citedMolecular biology & gene regulationOpenAlex
  3. VAEBAC: a representation-learning framework for proteome-scale prediction of amyloidogenic proteins and functional stratification of nucleic-acid-binding proteins.
    Muhammad Uzair Ashraf, Owais Ahmad, Rizwan Hasan Khan
    Bioinformatics (Oxford, England)Peer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCCrossref
  4. Precision Editing of Cis-Regulatory Elements Drives Crops Quantitative Traits Genetic Improvement: From Functional Dissection to Intelligent Design.
    Yulin Li, Xiangyu Zhang, Yongtao Cui +6
    Rice (New York, N.Y.)Peer-reviewedCC BY-NC-NDFull textMolecular biology & gene regulationEurope PMC
  5. Functional improvement of dystrophic muscle by utrophin gene editing
    Trinath Ghosh, SK Tousif Ahamed, Junchao Xu +6
    Molecular therapy. AdvancesPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCEurope PMCPMC

Cite

BibTeXRIS
BibTeX
@article{moen2026functional,
  title = {{Functional diversification of the cephalopod proteome by RNA-editing}},
  author = {Jack M. Moen and Alicia L. Richards and Einar K. Krogsaeter and Benjamin J. Polacco and Martin Gordon and Erica Stevenson and Rhiana Boyles and Maximilien Burq and Dejan Stepec and Bryan Crampton and Nathaniel Sin and Zachary Gale-Day and Jason E. Gestwicki and Peter Cimermancic and Joshua J. C. Rosenthal and Nevan J. Krogan and Danielle L. Swaney},
  journal = {Cell},
  year = {2026},
  month = oct,
  doi = {10.1016/j.cell.2026.09.043},
  url = {https://doi.org/10.1016/j.cell.2026.09.043},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Functional diversification of the cephalopod proteome by RNA-editing
AU  - Jack M. Moen
AU  - Alicia L. Richards
AU  - Einar K. Krogsaeter
AU  - Benjamin J. Polacco
AU  - Martin Gordon
AU  - Erica Stevenson
AU  - Rhiana Boyles
AU  - Maximilien Burq
AU  - Dejan Stepec
AU  - Bryan Crampton
AU  - Nathaniel Sin
AU  - Zachary Gale-Day
AU  - Jason E. Gestwicki
AU  - Peter Cimermancic
AU  - Joshua J. C. Rosenthal
AU  - Nevan J. Krogan
AU  - Danielle L. Swaney
PY  - 2026
DA  - 2026/10/15
JO  - Cell
DO  - 10.1016/j.cell.2026.09.043
UR  - https://doi.org/10.1016/j.cell.2026.09.043
AB  - Coleoid cephalopods exhibit the highest levels of adenosine deaminases acting on RNA (ADAR)-mediated RNA editing of any known taxon, yet the functional consequences of most recoding events remain unclear. Here, we integrated proteomics with biochemical and cellular assays to characterize recoding across the Doryteuthis pealeii proteome. This confirmed the translation of 7,997 recoded sites at the protein level and revealed how recoding reshapes the proteome by altering protein stability, subcellular localization, post-translational modifications, and enzymatic activity. We find that recoding also creates or ablates post-translational modification sites, with direct effects on protein function and protein-protein interactions. Recoding the E3 ligase MARCHF5 drives widespread changes in substrate ubiquitylation and perturbs mitochondrial homeostasis, illustrating how RNA editing can influence organelle function. Together, these data give a proteome-scale view of how extensive RNA recoding diversifies protein function in coleoid cephalopods and offer a framework for understanding how RNA-level plasticity shapes protein function and cellular physiology.
SN  - 0092-8674
SN  - 1097-4172
ER  -