Unanchored ubiquitin chains do not lead to marked alterations in gene expression in .
Jessica R Blount, Danielle N Meyer, Camille Akemann, Sean L Johnson, Katherine Gurdziel, Tracie R Baker, Sokol V Todi
Author Information
Jessica R Blount: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Danielle N Meyer: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Camille Akemann: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Sean L Johnson: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Katherine Gurdziel: Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Tracie R Baker: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA tracie.baker@wayne.edu stodi@wayne.edu.
Sokol V Todi: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA tracie.baker@wayne.edu stodi@wayne.edu. ORCID
The small protein modifier ubiquitin regulates various aspects of cellular biology through its chemical conjugation onto proteins. Ubiquitination of proteins presents itself in numerous iterations, from a single mono-ubiquitination event to chains of poly-ubiquitin. Ubiquitin chains can be attached onto other proteins or can exist as unanchored species, i.e. free from another protein. Unanchored ubiquitin chains are thought to be deleterious to the cell and rapidly disassembled into mono-ubiquitin. We recently examined the toxicity and utilization of unanchored poly-ubiquitin in We found that free poly-ubiquitin species are largely innocuous to flies and that free poly-ubiquitin can be controlled by being degraded by the proteasome or by being conjugated onto another protein as a single unit. Here, to explore whether an organismal defense is mounted against unanchored chains, we conducted RNA-Seq analyses to examine the transcriptomic impact of free poly-ubiquitin in the fly. We found ∼90 transcripts whose expression is altered in the presence of different types of unanchored poly-ubiquitin. The set of genes identified was essentially devoid of ubiquitin-, proteasome-, or autophagy-related components. The seeming absence of a large and multipronged response to unanchored poly-ubiquitin supports the conclusion that these species need not be toxic and underscores the need to re-examine the role of free ubiquitin chains in the cell.
