Abstract
RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.
Highlights
The abundance of the different eukaryotic RNA species controls cell type and cell fate, and is determined by the balance between RNA synthesis and RNA degradation
Cytosolic RNAs vary in their life-time, with messenger RNA (mRNA) encoding cell cycle regulators or transcription factors having reported life-times in the range of minutes (Geisberg et al, 2014; Miller et al, 2011), whereas ribosomal RNAs live for days (Turowski and Tollervey, 2015)
Of the decapping machinery occurs mainly after shortening of the polyA tail, which triggers decapping complex formation on the deadenylated 3 ́ end of mRNA and opening of the mRNA closed-loop structure (Caponigro and Parker, 1995; Morrissey et al, 1999). In this closed-loop model, the 50 and 30 ends of the mRNA are thought to be in close proximity by forming a complex between translation initiation factors binding to the 5 ́ cap and Pab1 associated with the 3 ́ end, thereby contributing to mRNA expression regulation (Vicens et al, 2018; Wells et al, 1998)
Summary
The abundance of the different eukaryotic RNA species controls cell type and cell fate, and is determined by the balance between RNA synthesis and RNA degradation. Of the decapping machinery occurs mainly after shortening of the polyA tail, which triggers decapping complex formation on the deadenylated 3 ́ end of mRNA and opening of the mRNA closed-loop structure (Caponigro and Parker, 1995; Morrissey et al, 1999) In this closed-loop model, the 50 and 30 ends of the mRNA are thought to be in close proximity by forming a complex between translation initiation factors binding to the 5 ́ cap and Pab associated with the 3 ́ end, thereby contributing to mRNA expression regulation (Vicens et al, 2018; Wells et al, 1998). Our dataset provides a rich resource for future studies of eukaryotic RNA degradation pathways, mechanisms, and the integration of mRNA metabolism
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