Global determinants of mRNA degradation rates in Saccharomyces cerevisiae

Abstract

Degradation of mRNA contributes to variation in transcript abundance. Studies of individual mRNAs show that cis and trans factors control mRNA degradation rates. However, transcriptome-wide studies have failed to identify global relationships between transcript properties and mRNA degradation. We investigated the contribution of cis and trans factors to transcriptome-wide degradation rate variation in the budding yeast, Saccharomyces cerevisiae, using multiple regression analysis. We find that multiple transcript properties are associated with mRNA degradation rates and that a model incorporating these factors explains [~]50% of the genome-wide variance. Predictors of mRNA degradation rates include transcript length, abundance, ribosome density, codon adaptation index (CAI) and GC content of the third position in codons. To validate these factors we studied individual transcripts expressed from identical promoters. We find that decreasing ribosome density by mutating the translational start site of the GAP1 transcript increases its degradation rate. Using variants of GFP that differ at synonymous sites, we show that increased GC content of the third position of codons results in decreased mRNA degradation rate. Thus, in steady-state conditions, a large fraction of genome-wide variation in mRNA degradation rates is determined by inherent properties of transcripts related to protein translation rather than specific regulatory mechanisms.