Publication: Stress-induced upregulation of the ubiquitin-relative Hub1 modulates pre-mRNA splicing and facilitates cadmium tolerance in Saccharomyces cerevisiae
Issued Date
2020-02-01
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ISSN
18792596
01674889
01674889
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2-s2.0-85074534097
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1867, No.2 (2020)
Suggested Citation
Sittinan Chanarat, Jisnuson Svasti Stress-induced upregulation of the ubiquitin-relative Hub1 modulates pre-mRNA splicing and facilitates cadmium tolerance in Saccharomyces cerevisiae. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1867, No.2 (2020). doi:10.1016/j.bbamcr.2019.118565 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/49535
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Title
Stress-induced upregulation of the ubiquitin-relative Hub1 modulates pre-mRNA splicing and facilitates cadmium tolerance in Saccharomyces cerevisiae
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Abstract
© 2019 Elsevier B.V. Splicing is a fundamental RNA-processing step for eukaryotic gene expression involved in the removal of intronic sequences of pre-mRNA. As the process is utilized for quantitative and qualitative regulation of gene expression, uncontrolled splicing can result in potential cellular dysfunctions. Accumulating evidence suggests that fidelity of splicing is regulated by a family of DEAD/DExH-box RNA helicases. Recently, we have shown that the evolutionarily-conserved ubiquitin-relative Hub1 binds directly to the DEAD-box RNA helicase Prp5, a key regulator of splicing fidelity, and stimulates its ATPase activity. When overexpressed, Hub1 enhances splicing efficiency and relaxes the constraints on splice-site and branch-site usages; yet physiological relevance of cellular Hub1 overexpression remains unknown. Here we show that Hub1 is upregulated at the transcriptional level via the yeast-specific AP1 regulon upon oxidative and heavy metal stresses, and promotes efficient splicing of introns with non-canonical splice-sites. While nonessential for yeast viability, Hub1 becomes important for cadmium tolerance when metallothionein-mediated defense system is impaired. Moreover, mutant variants of other splicing factors also showed a similar cadmium sensitivity, suggesting the role of splicing in facilitating tolerance of heavy metal stress. Taken together, we propose that cells adjust gene expression landscape required for heavy metal detoxification by promoting intron-specific splicing through the stress-induced overexpression of Hub1.