Author:
Acuña Myriah L.,García-Morin Andrea,Orozco-Sepúlveda Rebeca,Ontiveros Carlos,Flores Alejandra,Diaz Arely V.,Gutiérrez-Zubiate Isabel,Patil Abhijeet R.,Alvarado Luis A.,Roy Sourav,Russell William K.,Rosas-Acosta Germán
Abstract
AbstractSubstantial increases in the conjugation of the main human SUMO paralogs, SUMO1, SUMO2, and SUMO3, are observed upon exposure to different cellular stressors, and such increases are considered important to facilitate cell survival to stress. Despite their critical cellular role, little is known about how the levels of the SUMO modifiers are regulated in the cell, particularly as it relates to the changes observed upon stress. Here we characterize the contribution of alternative splicing towards regulating the expression of the main human SUMO paralogs under normalcy and three different stress conditions, heat-shock, cold-shock, and Influenza A Virus infection. Our data reveal that the normally spliced transcript variants are the predominant mature mRNAs produced from the SUMO genes and that the transcript coding for SUMO2 is by far the most abundant of all. We also provide evidence that alternatively spliced transcripts coding for protein isoforms of the prototypical SUMO proteins, which we refer to as the SUMO alphas, are also produced, and that their abundance and nuclear export are affected by stress in a stress- and cell-specific manner. Additionally, we provide evidence that the SUMO alphas are actively synthesized in the cell as their coding mRNAs are found associated with translating ribosomes. Finally, we provide evidence that the SUMO alphas are functionally different from their prototypical counterparts, with SUMO1α and SUMO2α being non-conjugatable to protein targets, SUMO3α being conjugatable but targeting a seemingly different subset of protein from those targeted by SUMO3, and all three SUMO alphas displaying different cellular distributions from those of the prototypical SUMOs. Thus, alternative splicing appears to be an important contributor to the regulation of the expression of the SUMO proteins and the cellular functions of the SUMOylation system.
Funder
US Department of Defense, US ARMY Peer Reviewed Medical Research Program
National Institute of General Medical Sciences
MARC program - National Institutes of Health
Research Centers in Minority Institutions program, National Institutes on Minority Health and Health Disparities (NIMHD), NIH
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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