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Article Dans Une Revue Nature Communications Année : 2023

N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity

Sylvia Varland
Rui Duarte Silva
Ine Kjosås
Alexandra Faustino
Annelies Bogaert
Michael Costanzo
Adrian Drazic
Katherine Chan
Xiang Zhang
Amy Hin Yan Tong
Simonetta Andreazza
Juliette J. Lee
Matej Usaj
Alexander J. Whitworth
Brenda j. Andrews
Jason Moffat
Chad l. Myers
Kris Gevaert
Charles Boone
Rui Gonçalo Martinho
Thomas Arnesen

Résumé

Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal strong genetic dependency between major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both ligase complex UBR4-KCMF1 NatC recognize bearing an unacetylated methionine followed by hydrophobic residue. KO-induced protein degradation phenotypes reversed UBR knockdown, demonstrating central cellular role of this interplay. We loss Drosophila is associated with male sterility, reduced longevity, age-dependent motility due to developmental muscle defects. Remarkably, muscle-specific overexpression UbcE2M, one targeted for KO-mediated degradation, suppresses defects deletion. In conclusion, NatC-mediated acetylation acts as protective mechanism against which relevant increased longevity motility.
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Dates et versions

hal-04284338 , version 1 (14-11-2023)

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Sylvia Varland, Rui Duarte Silva, Ine Kjosås, Alexandra Faustino, Annelies Bogaert, et al.. N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Nature Communications, 2023, 14 (1), pp.6774. ⟨10.1038/s41467-023-42342-y⟩. ⟨hal-04284338⟩
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