A Novel Role for Protein Kinase Kin2 in Regulating HAC1 mRNA Translocation, Splicing, and Translation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
A Novel Role for Protein Kinase Kin2 in Regulating HAC1 mRNA
Translocation, Splicing, and Translation
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| Creator |
Anshu, Ashish
Mannan, M. Amin-ul Chakraborty, Abhijit Chakrabarti, Saikat Dey, Madhusudan |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
A signaling network called the unfolded protein response (UPR) resolves the protein-folding defects in the endoplasmic reticulum (ER) from yeasts to humans. In the yeast Saccharomyces cerevisiae, the UPR activation involves (i) aggregation of the ERresident kinase/RNase Ire1 to form an Ire1 focus, (ii) targeting HAC1 pre-mRNA toward the Ire1 focus that cleaves out an inhibitory intron from the mRNA, and (iii) translation of Hac1 protein from the spliced mRNA. Targeting HAC1 mRNA to the Ire1 focus requires a cis-acting bipartite element (3=BE) located at the 3= untranslated leader. Here, we report that the 3=BE plays an
additional role in promoting translation from the spliced mRNA. We also report that a high dose of either of two paralogue kinases, Kin1 and Kin2, overcomes the defective UPR caused by a mutation in the 3=BE. These results define a novel role for Kin kinases in the UPR beyond their role in cell polarity and exocytosis. Consistently, targeting, splicing, and translation of HAC1 mRNA are substantially reduced in the kin1� kin2� strain. Furthermore, we show that Kin2 kinase domain itself is sufficient to activate the UPR, suggesting that Kin2 initiates a signaling cascade to ensure an optimum UPR.
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| Publisher |
American Society for Microbiology
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2240/1/MOLECULAR_AND_CELLULAR_BIOLOGY__V.__35__(_1_)_199%2D210;2015[101].pdf
Anshu, Ashish and Mannan, M. Amin-ul and Chakraborty, Abhijit and Chakrabarti, Saikat and Dey, Madhusudan (2015) A Novel Role for Protein Kinase Kin2 in Regulating HAC1 mRNA Translocation, Splicing, and Translation. Molecular and Cellular Biology, 35 (1). pp. 199-210. |
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| Relation |
http://dx.doi.org/10.1128/MCB.00981-14
http://www.eprints.iicb.res.in/2240/ |
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