GCN sensitive protein translation in yeast
| Autor: | Michael P. Weir, Daniel Krizanc, Karen Voelkel-Meiman, Jungwoo Cho, Kristen Scopino, Om K. Chatterji, Ruchi B. Sheth, William A. Barr, Jack Kwon, Kelly M. Thayer, Felix Hart, Jacob W. Glickman |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Protein Expression Codon Initiator Gene Expression Protein Structure Prediction Biochemistry Ribosome Macromolecular Structure Analysis Base Composition 0303 health sciences Multidisciplinary biology Nucleotides Chemistry Messenger RNA 030302 biochemistry & molecular biology Eukaryota Translation (biology) Genomics Cell biology DNA-Binding Proteins Nucleic acids Medicine Cellular Structures and Organelles Research Article Protein Structure Saccharomyces cerevisiae Proteins Gene prediction Science Saccharomyces cerevisiae Molecular Dynamics Simulation Research and Analysis Methods Open Reading Frames 03 medical and health sciences Ribosomal protein Gene Expression and Vector Techniques Genetics RNA Messenger Molecular Biology Techniques Gene Prediction Molecular Biology Gene 030304 developmental biology Molecular Biology Assays and Analysis Techniques Biology and life sciences Organisms Fungi Computational Biology Proteins Cell Biology Genome Analysis biology.organism_classification Yeast Repressor Proteins Open reading frame A-site Protein Biosynthesis RNA Protein Translation Ribosomes Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 9, p e0233197 (2020) |
| Popis: | Levels of protein translation by ribosomes are governed both by features of the translation machinery as well as sequence properties of the mRNAs themselves. We focus here on a striking three-nucleotide periodicity, characterized by overrepresentation of GCN codons and underrepresentation of G at the second position of codons, that is observed in Open Reading Frames (ORFs) of mRNAs. Our examination of mRNA sequences in Saccharomyces cerevisiae revealed that this periodicity is particularly pronounced in the initial codons--the ramp region--of ORFs of genes with high protein expression. It is also found in mRNA sequences immediately following non-standard AUG start sites, located upstream or downstream of the standard annotated start sites of genes. To explore the possible influences of the ramp GCN periodicity on translation efficiency, we tested edited ramps with accentuated or depressed periodicity in two test genes, SKN7 and HMT1. Greater conformance to (GCN)n was found to significantly depress translation, whereas disrupting conformance had neutral or positive effects on translation. Our recent Molecular Dynamics analysis of a subsystem of translocating ribosomes in yeast revealed an interaction surface that H-bonds to the +1 codon that is about to enter the ribosome decoding center A site. The surface, comprised of 16S/18S rRNA C1054 and A1196 (E. coli numbering) and R146 of ribosomal protein Rps3, preferentially interacts with GCN codons, and we hypothesize that modulation of this mRNA-ribosome interaction may underlie GCN-mediated regulation of protein translation. Integration of our expression studies with large-scale reporter studies of ramp sequence variants suggests a model in which the C1054-A1196-R146 (CAR) interaction surface can act as both an accelerator and braking system for ribosome translation. |
| Databáze: | OpenAIRE |
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