Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae
| Autor: | Biswadip Das, Debasish Sarkar, Sunirmal Paira |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Untranslated region Saccharomyces cerevisiae Proteins Transcription Genetic RNA Splicing RNA Stability Population Repressor Saccharomyces cerevisiae Biology Protein Serine-Threonine Kinases 03 medical and health sciences Gene Expression Regulation Fungal Genetics RNA Precursors education 3' Untranslated Regions Regulation of gene expression Cell Nucleus Messenger RNA education.field_of_study Membrane Glycoproteins Endoplasmic reticulum Gene regulation Chromatin and Epigenetics RNA Fungal Cell biology Repressor Proteins Kinetics 030104 developmental biology Basic-Leucine Zipper Transcription Factors Biochemistry RNA splicing Unfolded protein response Unfolded Protein Response |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Unfolded protein response (UPR) is triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which is accomplished by a dramatic induction of genes encoding ER chaperones. Activation of these genes involves their rapid transcription by Hac1p, encoded by the HAC1 precursor transcript harboring an intron and a bipartite element (3′-BE) in the 3′-UTR. ER stress facilitates intracellular targeting and recruitment of HAC1 pre-mRNA to Ire1p foci (requiring 3′-BE), leading to its non-spliceosomal splicing mediated by Ire1p/Rlg1p. A critical concentration of the pre-HAC1 harboring a functional 3′-BE element is governed by its 3′→5′ decay by the nuclear exosome/DRN. In the absence of stress, pre-HAC1 mRNA undergoes a rapid and kinetic 3′→5′ decay leading to a precursor pool, the majority of which lack the BE element. Stress, in contrast, causes a diminished decay, thus resulting in the production of a population with an increased abundance of pre-HAC1 mRNA carrying an intact BE, which facilitates its more efficient recruitment to Ire1p foci. This mechanism plays a crucial role in the timely activation of UPR and its prompt attenuation following the accomplishment of homeostasis. Thus, a kinetic mRNA decay provides a novel paradigm for mRNA targeting and regulation of gene expression. |
| Databáze: | OpenAIRE |
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