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- Title
Small-sample learning reveals propionylation in determining global protein homeostasis.
- Authors
Shui, Ke; Wang, Chenwei; Zhang, Xuedi; Ma, Shanshan; Li, Qinyu; Ning, Wanshan; Zhang, Weizhi; Chen, Miaomiao; Peng, Di; Hu, Hui; Fang, Zheng; Guo, Anyuan; Gao, Guanjun; Ye, Mingliang; Zhang, Luoying; Xue, Yu
- Abstract
Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct in-depth propionylomic profiling in Drosophila, and develop a small-sample learning framework to prioritize the propionylation at lysine 17 of H2B (H2BK17pr) to be functionally important. Mutating H2BK17 which eliminates propionylation leads to elevated total protein level in vivo. Further analyses reveal that H2BK17pr modulates the expression of 14.7–16.3% of genes in the proteostasis network, and determines global protein level by regulating the expression of genes involved in the ubiquitin-proteasome system. In addition, H2BK17pr exhibits daily oscillation, mediating the influences of feeding/fasting cycles to drive rhythmic expression of proteasomal genes. Our study not only reveals a role of lysine propionylation in regulating proteostasis, but also implements a generally applicable method which can be extended to other issues with little prior knowledge. The development of a new smallsample learning framework, KprFunc, leads to the discovery of an important role for lysine propionylation in determining global protein homeostasis, mediated by a critical propionylation site on histone H2B, H2BK17pr.
- Subjects
GENE regulatory networks; HOMEOSTASIS; PROTEINS; PROTEASOMES; LYSINE; DROSOPHILA
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38414-8