Functional diversification of the cephalopod proteome by RNA-editing

ABSTRACT: Coleoid cephalopods exhibit the highest levels of ADAR-mediated RNA editing in coding sequences of any known animal, yet the functional consequences of most recoding events remain largely unknown. Here we integrate proteomics with biochemical and cellular assays to characterize thousands of recoding events across the Doryteuthis pealeii proteome. Using quantitative and functional mass spectrometry, we show that RNA editing reshapes the cellular proteome to alter protein stability, subcellular localization, post-translational modifications, and enzymatic activity. We find that editing can regulate post-translational modifications through their creation or ablation, and this has direct effects on protein function. Editing of the E3 ligase MARCHF5 improves activity and promotes mitophagy, providing a mechanism by which editing can shape organelle function. These data provide the first proteome-scale view of how extensive RNA recoding diversifies protein function in coleoid cephalopods and offers a new framework for understanding how RNA-level plasticity shapes protein function and cellular physiology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Doryteuthis Pealeii

TISSUE(S): Optic Lobe, Gill, Cell Culture

SUBMITTER: Jack Moen  

LAB HEAD: Danielle L Swaney

PROVIDER: PXD078742 | Pride | 2026-10-09

REPOSITORIES: Pride