The Contribution of Alternative Splicing Toward the Global Control of SUMO1 Sumoylation
SUMOylation, the attachment of the Small Ubiquitin-like Modifier (SUMO) to a target protein, is a post-translational modification similar to that of Ubiquitination in terms of the cascade of events required to produce the final modified target. However, instead of targeting proteins for degradation, as Ubiquitination usually does, SUMOylation appears to regulate many vital cellular processes including nucleocytoplasmic transport, transcription, apoptosis, protein stability, response to stress, and progression through the cell cycle (Hay, R.T, 2005). This versatility exhibited by the SUMOylation system makes it an optimal target for viral manipulation, as our laboratory has previously described for Influenza A virus (Pal, S., Rosas-Acosta, G., 2009). It is presently acknowledged that the human genome contains at least five clearly distinct functional SUMO genes, namely SUMO1, 2, 3, 4 and 5 as well as various SUMO pseudogenes. Importantly, analysis of Homo sapiens SUMO1 sequences obtained from the NCBI database indicate the existence of three different processed mature mRNA transcripts for the SUMO1 gene, produced by alternative splicing, hereafter referred to as SUMO1 variants (var). While var1 and var2 are predicted to code for the protein typically thought of as SUMO1, var3 lacks exon 2 coding for an alternative SUMO1 isoform lacking a relatively short stretch of amino acids toward the N-terminus; this isoform will hereafter be referred to as SUMO1α. After performing an extensive review of published literature, we could not find any reports describing the existence of alternative SUMO1 isoforms. Furthermore, the existence of different mature mRNAs for SUMO1, while strongly supported by available RNA-Seq data, has not been actually reported in the primary scientific literature either. Hence, experimental confirmation of the existence of both, the different SUMO1 transcripts and the alternative SUMO1 isoform will be required to achieve a more thorough understanding of the molecular biology of SUMO1 and the mechanisms governing SUMO1 levels within the cell. Given the known "cyto-protective" properties of protein SUMOylation (Luo, J., Guo, C., 2017), an improved understanding of the contribution of such post-translational regulatory mechanisms to the global control of cellular SUMOylation may lead to the development of innovative therapies against conditions in which the cyto-protective 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 Toward the Global Control of SUMO1 Sumoylation" (2017). ETD Collection for University of Texas, El Paso. AAI10690079.