Hundreds of yeast mRNAs form a separately addressable, translation elongation-controlled regulon

Abstract

In addition to the widespread and well documented control of protein synthesis by translation initiation, recent evidence suggests that translation elongation can also control protein synthesis rates. One of the proposed mechanisms leading to elongation control is the interference of slow ribosome movement around the start codon with efficient translation initiation. Here we estimate the frequency with which this mode of control occurs in bakers yeast growing in rich medium. Genome-wide data reveal that transcripts from around 20% of yeast genes show evidence of queueing ribosomes, which may be indicative of translation elongation control. Moreover, this subset of transcripts is sensitive to distinct regulatory signals compared to initiation-controlled mRNAs, and such distinct regulation occurs for example during the response to osmotic stress. Notethe previous version 2 of this preprint contained a Decision-Tree based analysis where we attempted to relate mRNA features to the presence or absence of queueing ribosome peaks. Since releasing that version, we performed additional controls for this analysis which strongly sugest that its results are random and should be ignored. Specifically, both the overall predictability and the importance of individual features is very similar for a real dataset where genes are labelled as containing a second SSU peak or not, and for a simulated control dataset containing an equal proportion of randomly labelled genes. We have removed this figure from the current version. The analysis together with the additional control remains accessible on the accompanying Github repository (github.com/tobiasvonderhaar/ribosomespeedcontrol) in the file "Figure 3 Obsolete (Classification).ipynb".