Errors in macromolecular synthesis after stress. A study of the possible protective role of the small heat shock proteinsBiochemistry
Year: 2006
Type: dissertation
Abstract: The general goal of this thesis was to gain insight in what small heat shock proteins (sHsps) do with respect to macromolecular synthesis during a stressful situation in the cell. It is known that after a non-lethal heat shock, cells are better protected against a subsequent more severe heat shock, a phenomenon known as thermotolerance and attributed to the presence of the heat shock proteins. The question we asked first is whether the error rate in macromolecular synthesis (transcription, RNA processing, quality control mechanisms and translation) is increased during or after a heat shock in the cell. To know which of these processes might be failing in a cell during stress we designed different reporter systems and we studied the possible protective effect that the sHsps might have. We have shown that there is molecular misreading of sequence repeats and that this misreading is induced by stress. The sHsps did not prevent this. Concerning splicing, the sHsp Hsp27 provided a faster recovery of splicing after heat shock and a faster rephosphorylation of an inhibitor of splicing, dSRp38. Regarding mRNA quality control mechanisms, no defect in nonsense-mediated decay could be detected after heat shock. Finally we describe a relaxed stringency of AUG selection induced by heat shock. To determine whether the sHsps are able to help in cotranslational protein folding and/or heteromer formation, we examined the folding and assembly of beta-crystallins. In the lens, beta-crystallins are surrounded by a high concentration of the sHsp alpha-crystallin, so these are suitable model proteins to test if sHsps facilitate the folding of other crystallins in the lens, particularly that of heterodimeric crystallins. We described that the folding of betaA4-crystallin is helped by its heterodimeric partner, betaB2-crystallin, but not by sHsps
Author: L. Marin Vinader
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2171204944