UBB pseudogene 4 encodes functional ubiquitin variants.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32161257.
- Also identified by DOI 10.1038/s41467-020-15090-6 and PMC identifier 7066184.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes Ub<sup>KEKS</sup> (Q2K, K33E, Q49K, N60S). The functional consequences of Ub<sup>KEKS</sup> conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that Ub<sup>KEKS</sup> modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.
Medical subject headings
- Lamin Type A
- Pseudogenes
- Ubiquitin