Regulation of transcription and translation; A tale of crystallins and small heat shock proteins
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RU, Biochemistry, 7 januari 2005
Promotores : Jong, W.W.W. de, Zoelen, E.J.J. van Co-promotor : Lubsen, N.H.
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The DNA sequences of many genomes have been elucidated in the last years. The challenge now is to predict first the genotype and then the phenotype from the genomic sequences. To predict expression patterns of the genes located on the genome, not only regulation at the level of transcription, but also at the level of translation is important. To obtain more information about regulation of transcription, the promoter and its regulatory elements need to be mapped. In this thesis a conventional search for known and active regulatory elements in the B2-crystallin promoter was performed. For the intergenic region between aB-crystallin and HspB2, an alternative approach was taken to determine which elements are likely to be important for gene regulation, and the evolutionary conservation of sequence elements in this region was studied. Alignments of this region of many species lead to the confirmation of importance of known regulatory elements and the finding of new sites. A good example of regulation of gene expression mediated by regulation of translation, is translation after stress. During and after heat shock, cap-dependent translation is inhibited, while cap-independent translation can still take place. After heat shock translation of (s)Hsps is increased, these (s)Hsps are thought to protect cells from stress. We show that two of the sHsps, aB-crystallin and Hsp27 protect cap-dependent, but not cap-independent translation after heat shock. Inhibition of translation is thought to be mediated by a decrease in activity of the translation factors. However, the protection of translation mediated by sHsps does not seem to affect translation factors directly, but overexpression of aB-crystallin seems to increase the dispersal of stress granules that contain the stalled translation initiation complexes. We propose that aB-crystallin, probably together with other Hsps, resolubilizes the stress granule components and that translational thermotolerance is a cooperative effect of different Hsps.
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