The Contribution of Alternative Splicing and Post-Transcriptional Mechanisms Toward the Global Control of SUMO1/2/3 SUMOylation
Evolutionary pressures have caused eukaryotic cells to develop various response mechanisms to changing environments, particularly stress adaptations that have been inherited over time. SUMOylation, the post-translational conjugation of the Small Ubiquitin-like Modifiers to a lysine residue on target proteins, is well-documented to regulate essential processes within the cell, including nucleocytoplasmic transport, transcription, apoptosis, protein stability, and progression through the cell cycle (1). SUMO protein levels have been reported to increase upon diverse stress states, including viral infection (2), cardiovascular ischemic events (3), temperature shock (4), and cancer (5). However, very little is known about how SUMOylation is regulated within the cell, particularly how SUMO protein levels are rapidly increased upon stress. Analysis of human SUMO mRNA sequences obtained from the NCBI database indicates the existence of three different transcripts, or variants (var), for the SUMO1 gene and two distinct mature mRNA transcript variants for both the SUMO2 and SUMO3 genes. For each SUMO paralog, one of the variants described codes for a previously unidentified protein isoform displaying a slightly different amino acid sequence from that of the prototype paralog, hereafter referred to as the α- isoform. To achieve a more thorough understanding of the molecular biology and the mechanisms governing SUMO protein levels within the cell, in these studies we establish the relative abundance of both the regular and alternative transcripts coding for the main SUMO paralogs in human cells, SUMO1, SUMO2, and SUMO3, under normal and stress conditions. For all three SUMOs, the variant transcripts that code for the well-characterized protein isoforms appears to be the most abundant transcripts. In contrast, the one coding for the α-isoforms tends to change upon stress. Given the known cytoprotective properties of protein SUMOylation (6), an improved understanding of the contribution of such post-transcriptional mechanisms to the regulation of SUMOylation may lead to the development of innovative therapies for conditions in which the role of protein SUMOylation plays a critical function in host survival, including infectious diseases such as Influenza A virus infection, and cardiovascular ischemic events such as strokes and heart attacks.
Acuña, Myriah Lorraine, "The Contribution of Alternative Splicing and Post-Transcriptional Mechanisms Toward the Global Control of SUMO1/2/3 SUMOylation" (2022). ETD Collection for University of Texas, El Paso. AAI29209132.