Characterization of messenger ribonucleoproteincomplexes (mRNPs) during cellular stresses
Final Report Abstract
Cells have to adapt to the constantly changing environment and cope with situations such as starvation and osmotic or temperature stresses. Although these situations can be very different, the adaptation process always has in common that the cellular expression pattern changes rapidly, allowing cells to cope with the stress situation and to survive. To accomplish that quickly, bulk mRNA export from the nucleus to the cytoplasm is blocked and only the selective export of stress specific mRNAs is supported. Those are then preferentially translated at the ribosomes. The mechanisms of how this is accomplished were largely unknown and investigated within this project. In Saccharomyces cerevisiae, the shuttling RNA adapterproteins Npl3, Gbp2, Hrb1 and Nab2 are loaded co-transcriptionally onto the growing pre-mRNA. Prior to export they recruit the export-receptor heterodimer Mex67-Mtr2 (TAP-p15 in human) to allow subsequent export. Here, we show that cellular stress induces the dissociation of Mex67 from regular mRNAs by removal of its adapter-proteins to prevent general mRNA export. At the same time, HS-mRNAs are rapidly exported in direct association with Mex67, without the need for adapter-proteins. The immediate cotranscriptional loading of Mex67 onto HS-mRNAs involves the heat shock transcription factor Hsf1, which binds to heat shock promoter elements (HSEs) in stress responsive genes. Importantly, we show that the difference between both export modes is, that adapter-protein bound mRNAs are quality controlled, while the export of stress-specific transcripts is not. In fact, a regular, non-HS-mRNA is converted into an uncontrolled stress-responsive transcript by expression from a HS-promoter, suggesting that the fate of being quality controlled is encrypted in the promoter. Therefore, under normal conditions, Mex67-adapterproteins are recruited for RNA surveillance, allowing only quality controlled mRNAs to associate with Mex67 and to leave the nucleus. Thus, at the cost of an error-free mRNA formation, HS-mRNAs are exported and translated without the least delay, which allows cells to survive extreme situations.
Publications
- (2014) Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1. Nat Commun. 5:3123
Hackmann A., Wu H., Schneider UM., Meyer K., Jung K. and Krebber H.
(See online at https://doi.org/10.1038/ncomms4123) - (2016) mRNA quality control is bypassed for an immediate export of stress responsive transcripts. Nature, 540: 593-596
Zander, G., Hackmann, A., Bender, L., Becker, D., Lingner, T., Salinas, G. and Krebber, H.
(See online at https://doi.org/10.1038/nature20572)
