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Alternative splicing is a prevalent mechanism of gene regulation that is modulated in response to a wide range of extracellular stimuli. Stress-activated protein kinases (SAPKs) play a key role in controlling several steps of mRNA biogenesis. Here, we show that osmostress has an impact on the regulation of alternative splicing (AS), which is partly mediated through the action of p38 SAPK. Splicing network analysis revealed a functional connection between p38 and the spliceosome component SKIIP, whose depletion abolished a significant fraction of p38-mediated AS changes. Importantly, p38 interacted with and directly phosphorylated SKIIP, thereby altering its activity. SKIIP phosphorylation regulated AS of GADD45α, the upstream activator of the p38 pathway, uncovering a negative feedback loop involving AS regulation. Our data reveal mechanisms and targets of SAPK function in stress adaptation through the regulation of AS.
Pubmed ID: 30995481 RIS Download
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Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets Raised against a peptide mapping to C-terminus of GADD45 of human origin (Homologues in Mouse)
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View all literature mentionsThis polyclonal targets MAPK14
View all literature mentionsThis unknown targets T7•Tag® Agarose
View all literature mentionsThis polyclonal targets Skip (H-300)
View all literature mentionsThis monoclonal targets HNRNPA1
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis unknown targets T7•Tag® Agarose
View all literature mentionsThis polyclonal targets Skip (H-300)
View all literature mentionsThis polyclonal targets T7
View all literature mentionsThis monoclonal targets HNRNPA1
View all literature mentionsThis unknown targets Raised against a peptide mapping to C-terminus of GADD45 of human origin (Homologues in Mouse)
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis monoclonal targets HNRNPA1
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets T7•Tag® Agarose
View all literature mentionsThis polyclonal targets MAPK14
View all literature mentionsThis unknown targets Raised against a peptide mapping to C-terminus of GADD45 of human origin (Homologues in Mouse)
View all literature mentionsThis polyclonal targets Skip (H-300)
View all literature mentionsThis polyclonal targets T7
View all literature mentionsThis monoclonal targets GAPDH (6C5)
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