UBB pseudogene 4 encodes functional ubiquitin variants

被引：42

作者：

Dubois, Marie-Line ^{[1
]}

Meller, Anna ^{[1
]}

Samandi, Sondos ^{[2
]}

Brunelle, Mylene ^{[2
]}

Frion, Julie ^{[1
]}

Brunet, Marie A. ^{[2
]}

Toupin, Amanda ^{[2
]}

Beaudoin, Maxime C. ^{[2
]}

Jacques, Jean-Francois ^{[2
]}

Levesque, Dominique ^{[1
]}

Scott, Michelle S. ^{[2
]}

Lavigne, Pierre ^{[2
]}

Roucou, Xavier ^{[2
]}

Boisvert, Francois-Michel ^{[1
]}

机构：

[1] Dept Immunol & Cell Biol, Sherbrooke, PQ, Canada

[2] Dept Biochem & Funct Genom, Sherbrooke, PQ, Canada

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ABSOLUTE QUANTIFICATION; AFFINITY PURIFICATION; PROTEIN EXPRESSION; BINDING; GENE; IDENTIFICATION; LIGASES; GENOME; MECHANISMS; REGULATORS;

D O I：

10.1038/s41467-020-15090-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(KEKS) (Q2K, K33E, Q49K, N60S). The functional consequences of Ub(KEKS) conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that Ub(KEKS) 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. Ubiquitin pseudogenes are present in many organisms but whether they encode functional proteins has remained unclear. Here, the authors show that human UBB pseudogene 4 produces ubiquitin variants with amino acid compositions and cellular functions that are distinct from canonical ubiquitin.

引用

页数：12

共 69 条

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