Molecular background of HAC1-driven improvement in the secretion of recombinant protein in based on comparative transcriptomics.

While the unfolded protein response (UPR) and its major regulator - transcription factor Hac1 are well-conserved across , species-specific variations are repeatedly reported. Here we investigated molecular mechanisms by which co-over-expression of improves secretion of a recombinant protein (r-Prot) in , using comparative transcriptomics. Co-over-expression of caused an >2-fold increase in secreted r-Prot, but its intracellular levels were decreased. The unconventional splicing rate of the mRNA was counted through transcript sequencing. Multiple biological processes were affected in the -and-r-Prot co-over-expressing strain, including ribosome biogenesis, nuclear and mitochondrial events, cell cycle arrest, attenuation of gene expression by RNA polymerase III and II, as well as modulation of proteolysis and RNA metabolism; but whether the co-over-expression/induction was the actual causative agent for these changes, was not always clear. We settled that the expression of the "conventional" targets ( and ) is not affected by its over-expression.