Quantitating translational control: mRNA abundance-dependent and independent contributions and the mRNA sequences that specify them.

Abstract

Translation rate per mRNA molecule correlates positively with mRNA abundance. As a result, protein levels do not scale linearly with mRNA levels, but instead scale with the abundance of mRNA raised to the power of an ‘amplification exponent’. Here we show that to quantitate translational control, the translation rate must be decomposed into two components. One, TRmD, depends on the mRNA level and defines the amplification exponent. The other, TRmIND, is independent of mRNA amount and impacts the correlation coefficient between protein and mRNA levels. We show that in Saccharomyces cerevisiae TRmD represents ∼20% of the variance in translation and directs an amplification exponent of 1.20 with a 95% confidence interval [1.14, 1.26]. TRmIND constitutes the remaining ∼80% of the variance in translation and explains ∼5% of the variance in protein expression. We also find that TRmD and TRmIND are preferentially determined by different mRNA sequence features: TRmIND by the length of the open reading frame and TRmD both by a ∼60 nucleotide element that spans the initiating AUG and by codon and amino acid frequency. Our work provides more appropriate estimates of translational control and implies that TRmIND is under different evolutionary selective pressures than TRmD.