Cytoplasmic 5′-3′ exonuclease Xrn1p is also a genome-wide transcription factor in yeast

TLDR

Xrn1 is a large exoribonuclease essential for cytoplasmic mRNA degradation, and although its deletion is non‑lethal, it alters mRNA synthesis and stability, with decaysome components also acting as nuclear transcriptional regulators. The study aims to show that loss of Xrn1 activity selectively perturbs synthesis and decay of a specific mRNA subset and to define these genes as the Xrn1 synthegradon. The authors disrupted Xrn1 activity and assessed its impact on mRNA synthesis and decay rates. Xrn1 preferentially regulates highly expressed ribosomal and translation factor genes, acting as a synthegradase that coordinates protein synthesis machinery expression.

Abstract

The 5’ to 3’ exoribonuclease Xrn1 is a large protein involved in cytoplasmatic mRNA degradation as a critical component of the major decaysome. Its deletion in the yeast Saccharomyces cerevisiae is not lethal, but it has multiple physiological effects. In a previous study, our group showed that deletion of all tested components of the yeast major decaysome, including XRN1, results in a decrease in the synthetic rate and an increase in half-life of most mRNAs in a compensatory manner. Furthermore, the same study showed that the all tested decaysome components are also nuclear proteins that bind to the 5’ region of a number of genes. In the present work, we show that disruption of Xrn1 activity preferentially affects both the synthesis and decay of a distinct subpopulation of mRNAs. The most affected mRNAs are the transcripts of the highly transcribed genes, mainly those encoding ribosome biogenesis and translation factors. Previously, we proposed that synthegradases play a key role in regulating both mRNA synthesis and degradation. Evidently, Xrn1 functions as a synthegradase, whose selectivity might help coordinating the expression of the protein synthetic machinery. We propose to name the most affected genes “Xrn1 synthegradon”.