Temperature-dependent RNA editing in octopus extensively recodes the neural proteome

• Published in: Cell Vol. 186; no. 12; pp. 2544 - 2555.e13
• Main Authors: Birk, Matthew A., Liscovitch-Brauer, Noa, Dominguez, Matthew J., McNeme, Sean, Yue, Yang, Hoff, J. Damon, Twersky, Itamar, Verhey, Kristen J., Sutton, R. Bryan, Eisenberg, Eli, Rosenthal, Joshua J.C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.06.2023
• Subjects: acclimation; ADAR; Adenosine Deaminase - metabolism; Animals; cephalopod; epitranscriptome; kinesin; Nervous System - metabolism; neural plasticity; Octopodiformes - genetics; Proteome - metabolism; RNA - metabolism; RNA Editing; RNA modifications; synaptotagmin; Temperature; RNA editing; cephalopod; neural plasticity; kinesin; acclimation; temperature; ADAR; epitranscriptome; synaptotagmin; RNA modifications
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2023.05.004

In poikilotherms, temperature changes challenge the integration of physiological function. Within the complex nervous systems of the behaviorally sophisticated coleoid cephalopods, these problems are substantial. RNA editing by adenosine deamination is a well-positioned mechanism for environmental acclimation. We report that the neural proteome of Octopus bimaculoides undergoes massive reconfigurations via RNA editing following a temperature challenge. Over 13,000 codons are affected, and many alter proteins that are vital for neural processes. For two highly temperature-sensitive examples, recoding tunes protein function. For synaptotagmin, a key component of Ca2+-dependent neurotransmitter release, crystal structures and supporting experiments show that editing alters Ca2+ binding. For kinesin-1, a motor protein driving axonal transport, editing regulates transport velocity down microtubules. Seasonal sampling of wild-caught specimens indicates that temperature-dependent editing occurs in the field as well. These data show that A-to-I editing tunes neurophysiological function in response to temperature in octopus and most likely other coleoids. [Display omitted] •Octopus bimaculoides increase A-to-I RNA editing at >20,000 sites in the cold•Editing shifts occur within hours and are observed in wild populations•As a functional example, one cold-induced site alters kinesin motility•Another cold-induced site alters Ca2+-binding affinity of synaptotagmin Octopuses utilize RNA editing to rapidly respond to environmental temperature changes by altering protein function.