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

Daniel A Medina,Antonio Jordán-Pla,José E Pérez-Ortín,Mordechai Choder,Gonzalo Millán-Zambrano,Sebastián Chávez

doi:10.3389/fgene.2014.00001

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.”

Highlights

Xrn1 is a pleiotropic eukaryotic protein (Kim and Kim, 2002) involved in several RNA processing and degradation processes, such as general mRNA decay pathways (Muhlrad et al, 1994, 1995), surveillance mechanisms for aberrant mRNAs (He et al, 2003) and tRNAs (Wichtowska et al, 2013), processing intron lariats after splicing and ncRNA processing and degradation. It is dispensable for viability in optimally proliferating yeast, Drosophila and Arabidopsis, but its absence brings about pleiotropic effects that relate specially with both development in higher eukaryotes and growth control in lower eukaryotes (Kim and Kim, 2002; Jones et al, 2012; Nagarajan et al, 2013)
The second method is based on an indirect calculation of the degradation rate for each mRNA by assuming that it is equal to the synthesis rate (Pérez-Ortín et al, 2012, 2013) because a steady state for mRNA concentrations exists during yeast exponential growth in YPD (Pelechano and Pérez-Ortín, 2010)
Using BioGRO, we found that the average BioGRO map along genes bodies shows that the level of active RNA pol II, from the start site to the end, is lower in the xrn1 than in the wt (Figure 6B), which is compatible with the reduction in transcription initiation postulated using CHROMATIN IMMUNO-PRECIPITATION (ChIP)-exo data in Xr1p binding (Haimovich et al, 2013)

Summary

Introduction

Xrn ( called Kem in yeast, Pacman in Drosophila, and XRN4 in Arabidopsis) is a pleiotropic eukaryotic protein (Kim and Kim, 2002) involved in several RNA processing and degradation processes, such as general mRNA decay pathways (Muhlrad et al, 1994, 1995), surveillance mechanisms for aberrant mRNAs (He et al, 2003) and tRNAs (Wichtowska et al, 2013), processing intron lariats after splicing and ncRNA processing and degradation (reviewed in Nagarajan et al, 2013). The specificity of Arabidopsis XRN4 (Rymarquis et al, 2011) and animal XRN1 (Orban and Izaurralde, 2005) on certain types of transcripts has led to the suggestion that its major role is not bulk decay, but the control of developmental programs. These general phenotypes have been related with the large number of mRNAs whose stability and levels are affected in xrn mutants or with “downstream” indirect effects (Nagarajan et al, 2013)

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Conclusion