Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation

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dc.citation.volumeAccepted Manuscript
dc.contributor.authorShanmugam R
dc.contributor.authorAnderson R
dc.contributor.authorSchiemann AH
dc.contributor.authorSattlegger E
dc.coverage.spatialEngland
dc.date.accessioned2024-03-11T23:02:28Z
dc.date.accessioned2024-07-25T06:51:41Z
dc.date.available2024-03-05
dc.date.available2024-03-11T23:02:28Z
dc.date.available2024-07-25T06:51:41Z
dc.date.issued2024-03-05
dc.description.abstractThe protein kinase Gcn2 and its effector protein Gcn1 are part of the General Amino Acid Control signalling (GAAC) pathway best known in yeast for its function in maintaining amino acid homeostasis.  Under amino acid limitation, Gcn2 becomes activated, subsequently increasing the levels of phosphorylated eIF2α (eIF2α-P).  This leads to the increased translation of transcriptional regulators, such as Gcn4 in yeast and ATF4 in mammals, and subsequent re-programming of the cell's gene transcription profile, thereby allowing cells to cope with starvation.  Xrn1 is involved in RNA decay, quality control and processing.  We found that Xrn1 co-precipitates Gcn1 and Gcn2, suggesting that these three proteins are in the same complex.  Growth under starvation conditions was dependent on Xrn1 but not on Xrn1-ribosome association, and this correlated with reduced eIF2α-P levels.  Constitutively active Gcn2 leads to a growth defect due to eIF2α-hyperphosphorylation, and we found that this phenotype was independent of Xrn1, suggesting that xrn1 deletion doesn't enhance eIF2α de-phosphorylation.  Our study provides evidence that Xrn1 is required for efficient Gcn2 activation, directly or indirectly.  Thus, we have uncovered a potential new link between RNA metabolism and the GAAC.
dc.description.confidentialfalse
dc.format.paginationBCJ20220531-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/38440860
dc.identifier.citationShanmugam R, Anderson R, Schiemann AH, Sattlegger E. (2024). Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.. Biochem J. Accepted Manuscript. (pp. BCJ20220531-).
dc.identifier.doi10.1042/BCJ20220531
dc.identifier.eissn1470-8728
dc.identifier.elements-typejournal-article
dc.identifier.issn0264-6021
dc.identifier.pii234172
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/71046
dc.languageeng
dc.publisherPortland Press on behalf of the Biochemical Society
dc.publisher.urihttps://portlandpress.com/biochemj/article/doi/10.1042/BCJ20220531/234172/Evidence-that-Xrn1-is-in-complex-with-Gcn1-and-is
dc.relation.isPartOfBiochem J
dc.rights(c) The author/sen
dc.subjectGcn1
dc.subjectGcn2
dc.subjectMolecular Biology
dc.subjectSacharomyces cerevisiae
dc.subjectXrn1
dc.subjectstarvation signaling
dc.titleEvidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation
dc.typeJournal article
pubs.elements-id487074
pubs.organisational-groupOther
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