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Cited by 19Ubiquitin and proteasome pathwaysRNA Research and SplicingHeat shock proteins research

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Alternative splicing of the SUMO1/2/3 transcripts affects cellular SUMOylation and produces functionally distinct SUMO protein isoforms

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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·2023·Scientific Reports
DOI 10.1038/s41598-023-29357-7PMC PMC9911741

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Abstract

Substantial 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.

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Metadata

Authors
Acuña, M. L., García-Morin, A., Orozco-Sepúlveda, R., Ontiveros, C., Flores, A., Diaz, A. V., Gutiérrez-Zubiate, I., Patil, A. R., Alvarado, L. A., Roy, S., Russell, W. K., & Rosas-Acosta, G.
Affiliations
  • The University of Texas at El Paso (US)
  • University of Pennsylvania (US)
  • Texas Tech University Health Sciences Center (US)
  • The University of Texas Medical Branch at Galveston (US)
Corresponding author
Rosas-Acosta, Germán
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-02-09
Volume
13
Issue
1
Pages
2309-2309
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-29357-7
PMC
PMC9911741
OpenAlex
W4319748084
Cited by
19
References
3
Citations by year
2026: 3 · 2025: 11 · 2024: 5
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • US Department of Defense, US ARMY Peer Reviewed Medical Research Program (W81XWH-20-1-0088)
  • National Institute of General Medical Sciences (RL5GM118969, TL4GM118971, UL1GM118970)
  • MARC program - National Institutes of Health (2T34GM008048)
  • Research Centers in Minority Institutions program, National Institutes on Minority Health and Health Disparities (NIMHD), NIH (2G12MD007592)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
alternative splicing, SUMOylation, SUMO1, SUMO2, SUMO3, heat shock, cold shock, influenza A virus infection, cellular stress response, nuclear export, protein conjugation, subcellular localization
MeSH terms
Genes, Regulator, Humans, Alternative Splicing, Protein Isoforms, Small Ubiquitin-Related Modifier Proteins, SUMO-1 Protein, Sumoylation

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