The yeast ALG7 gene functions by initiating the synthesis of the dolichol-linked oligosaccharide precursor and plays an important role in the control of protein N-glycosylation. The levels of ALG7 multiple transcripts are modulated by the physiological status of the cell and environmental cues, and deregulation of their abundance is deleterious to several cellular functions. Since ALG7 mRNAs are unstable, we investigated the role of these transcripts' half-lives in determining their steady-state levels. Using a temperature-sensitive RNA polymerase II mutant, we demonstrate that increased stability was the primary determinant of higher ALG7 mRNA abundance in response to glucose limitation or treatment with tunicamycin. In contrast, at the G1/G0 transition point, changes in the decay rates were inversely related to ALG7 transcript accumulation: the decreased abundance of ALG7 mRNAs following exit from the mitotic cycle was associated with lengthening of the decay rates, while their increased accumulation after growth stimulation correlated with decreased stability. This suggests that, depending on the circumstance, mRNA half-lives can either directly determine the level of ALG7 transcript accumulation or oppose regulatory changes at other control levels.
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http://dx.doi.org/10.1023/a:1006803004151 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Delivery of secretomes, which includes growth factors, cytokines, and mRNA, is critical in regenerative medicine for cell-to-cell communication. However, the harsh in vivo environment presents significant challenges for secretome delivery. Proteolytic enzymes shorten secretomes' half-lives, and secretomes tend to rapidly diffuse at defect sites.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control.
View Article and Find Full Text PDFToxicol Appl Pharmacol
December 2024
Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts, Lowell, MA, USA.
Perfluoroalkyl substances (PFAS) are a major public health concern, in part because several PFAS have elimination half-lives on the order of years and are associated with adverse health outcomes. While PFAS can be transported into bile, their efficient reuptake by intestinal transporter proteins results in minimal fecal elimination. Here, we tested the hypothesis that consumption of oat β-glucan, a dietary supplement known to disrupt the enterohepatic recirculation of bile acids, will reduce PFAS body burdens.
View Article and Find Full Text PDFMol Syst Biol
December 2024
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology, Berlin, Germany.
Chembiochem
November 2024
Screening and Compound Profiling, Quantitative Biosciences, Merck & Co., Inc., Rahway, New Jersey, 07065, USA.
Oral delivery of peptide therapeutics is limited by degradation by gut proteases like chymotrypsin. Existing databases of peptidases are limited in size and do not enable systematic analyses of protease substrate preferences, especially for non-natural amino acids. Thus, stability optimization of hit compounds is time and resource intensive.
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