RNA recoding in cephalopods tailors microtubule motor protein function

• Published in: Cell 2023-06, Vol.186 (12), p.2531-2543.e11
• Main Authors: Rangan, Kavita J., Reck-Peterson, Samara L.
• Format: Article
• Language: English
• Subjects: acclimation; Animals; cephalopod; Cephalopoda - genetics; Cephalopoda - metabolism; dynein; Dyneins - genetics; Dyneins - metabolism; epigenetics; kinesin; Kinesins - genetics; Kinesins - metabolism; microtubule; Microtubule Proteins; Microtubules - metabolism; Myosins - metabolism; Proteins - metabolism; RNA - metabolism; RNA editing; RNA recoding; squid; temperature
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2023.04.032

RNA editing is a widespread epigenetic process that can alter the amino acid sequence of proteins, termed “recoding.” In cephalopods, most transcripts are recoded, and recoding is hypothesized to be an adaptive strategy to generate phenotypic plasticity. However, how animals use RNA recoding dynamically is largely unexplored. We investigated the function of cephalopod RNA recoding in the microtubule motor proteins kinesin and dynein. We found that squid rapidly employ RNA recoding in response to changes in ocean temperature, and kinesin variants generated in cold seawater displayed enhanced motile properties in single-molecule experiments conducted in the cold. We also identified tissue-specific recoded squid kinesin variants that displayed distinct motile properties. Finally, we showed that cephalopod recoding sites can guide the discovery of functional substitutions in non-cephalopod kinesin and dynein. Thus, RNA recoding is a dynamic mechanism that generates phenotypic plasticity in cephalopods and can inform the characterization of conserved non-cephalopod proteins. [Display omitted] •RNA editing in squid specifies unique kinesin protein variants in different tissues•Unique kinesin variants are made acutely in response to seawater temperature•Cold-specific kinesin variants have enhanced single molecule motility in the cold•Cephalopod editomes can reveal functional substitutions in non-cephalopod proteins RNA recoding in squid specifies unique kinesin variants with distinct activities in different tissues and in response to changes in seawater temperature, and cephalopod recoding sites provide a guide to identifying functional substitutions in non-cephalopod motor proteins.