A key aspect of the control of gene expression is the differential rates of mRNA translation and degradation, including alterations due to extracellular inputs. Surprisingly, multiple examples now argue that Hsp70 protein chaperones and their associated Hsp40 partners modulate both mRNA degradation and translation. Hsp70 proteins affect mRNA metabolism by various mechanisms including regulating nascent polypeptide chain folding, activating signal transduction pathways, promoting clearance of stress granules, and controlling mRNA degradation in an mRNA-specific manner. Taken together, these observations highlight the general principle that mRNA metabolism is coupled to the proteostatic state of the cell, often as assessed by the presence of unfolded or misfolded proteins. The proper control of the proteome (proteostasis) and transcriptome (ribostasis) is critical to cell function.By multiple mechanisms, Hsp70 family members sense perturbation of proteostasis and then modulate aspects of mRNA metabolism.Hsp70 family members promote nascent protein folding and when defective this leads to inhibition of translation elongation.Hsp70 family members can be titrated by unfolded proteins leading to the activation of stress responsive signal transduction systems that modulate the transcriptome.Hsp70 family members can modulate the protein composition of individual mRNPs, thereby affecting their function.Hsp70 proteins promote disassembly of stress granules and are important for recovery of translation after stress.
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