Korpys-Woźniak Paulina, Celińska Ewelina
Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, ul. Wojska Polskiego 48, 60-637 Poznań, Poland.
Biotechnol Rep (Amst). 2023 May 8;38:e00801. doi: 10.1016/j.btre.2023.e00801. eCollection 2023 Jun.
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.
虽然未折叠蛋白反应（UPR）及其主要调节因子——转录因子Hac1在各物种间高度保守，但物种特异性差异仍屡有报道。在此，我们利用比较转录组学研究了在酿酒酵母中，共过表达Xbp1提高重组蛋白（r-Prot）分泌的分子机制。共过表达Xbp1使分泌的r-Prot增加了2倍以上，但其细胞内水平却降低了。通过转录测序计算Xbp1 mRNA的非常规剪接率。在共过表达Xbp1和r-Prot的菌株中，多个生物学过程受到影响，包括核糖体生物合成、细胞核和线粒体事件、细胞周期停滞、RNA聚合酶III和II对基因表达的减弱，以及蛋白水解和RNA代谢的调节；但Xbp1共过表达/诱导是否是这些变化的实际致病因素，并不总是明确的。我们确定“常规”Xbp1靶标（PTC和HAC1）的表达不受其过表达的影响。
