Modeling of mRNA deadenylation rates reveal a complex relationship between mRNA deadenylation and decay

Abstract

Complete cytoplasmic polyadenosine tail (polyA-tail) deadenylation is thought to be essential for initiating mRNA decapping and subsequent degradation. To investigate this prevalent model, we conducted direct RNA sequencing of S. cerevisiae mRNAs derived from chase experiments under steady-state and stress condition. Subsequently, we developed a numerical model based on a modified gamma distribution function, which estimated the transcriptomic deadenylation rate at 10 A/min. A simplified independent method, based on the delineation of quantile polyA-tail values, showed a correlation between the decay and deadenylation rates of individual mRNAs, which appeared consistent within functional transcript groups and associated with codon optimality. Notably, these rates varied during the stress response. Detailed analysis of ribosomal protein-coding mRNAs (RPG mRNAs), constituting 40% of the transcriptome, singled out this transcript group. While deadenylation and decay of RPG mRNAs accelerated under heat stress, their degradation could proceed even when deadenylation was blocked, depending entirely on ongoing nuclear export. Our findings support the general primary function of deadenylation in dictating the onset of decapping, while also demonstrating complex relations between these processes.mRNA decapping and subsequent degradation is believed to depend on polyA-tail deadenylation rates. New methods for modeling deadenylation rates find them to correlate with decapping for most yeast mRNAs. However, ribosomal protein transcripts can decay independently of deadenylation.The yeast in vivo deadenylation reaction can be described by a modified gamma model, which calculates the transcriptomic enzymatic deadenylation rate of 10 A/min.The deadenylation rates per transcript can be inferred from changes in polyA-tail distribution quantile values.Deadenylation and decay rates in correlate positively at steady-state and change under stress conditions, suggesting a functional link.mRNAs encoding for ribosomal proteins can decay independently of deadenylation.New methods for modeling deadenylation rates find them to correlate with decapping for most yeast mRNAs, except for ribosomal protein transcripts that can decay independently of deadenylation.