Title: More ubiquitins than meets the eye: Novel variants encoded by ubiquitin pseudogenes.
Professor, Department of Immunology and Cell Biology. Director of the Cancer Research Institute of the Universite de Sherbrooke. Faculty of Medicine and Health Sciences.
Abstract: Post-translational modification by ubiquitin and ubiquitin-like modifier proteins regulate cellular processes at almost every levels. Ubiquitin itself is encoded by four different genes: the UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27A, respectively, and UBB and UBC genes code for polyubiquitin precursors. Early studies identified several additional genes potentially coding for ubiquitin, but they were considered pseudogenes due to differences in amino acids compared to ubiquitin. Through analysis of large-scale proteomics and RNA sequencing experiments, we found evidence for expression at the mRNA and protein levels of several of the ubiquitin pseudogenes. Our results show that UBBP4, a pseudogene of the UBB subfamily, produces functional ubiquitin proteins with slightly different amino acids composition compared to the canonical sequence, and includes additional lysines. These ubiquitins variants are covalently conjugated to proteins that are different from ubiquitin, and proteins modified by UBBP4 are not targeted for proteasomal degradation. Interestingly, we have identified different protein targets including proteins involved in DNA replication and cell cycle progression when comparing UBBP4 with the canonical ubiquitin, demonstrating a specificity in the choice of protein substrates, and suggesting a different role for these novel ubiquitin variants. This implies that a subset of E3 ligases can specifically recognize these ubiquitin variants, and underlines the fact that some of the reported ubiquitin targets could rather be through these variants arising from wrongly annotated pseudogenes. Moreover, knockout of UBBP4 through CRISPR/Cas9 results in reduced cell growth and mislocalization of nuclear proteins. The identification of additional ubiquitin variants thus entails a new layer of complexity in protein regulation by ubiquitylation that has been unnoticed until now.
Monday, March 21, 2022 at 2:30 pm at LSC 3 and Zoom
Hosted by: Dr. Leonard Foster