Abstract
Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes.
Highlights
The dynamics of the transcriptome in response to environmental changes is governed by two opposing processes – RNA production, namely transcription, and RNA degradation
Organisms alter genes expression programs in response to changes in their environment. Such programs can specify fast induction, slow relaxation, oscillations, etc. These kinetic outputs may depend on proper orchestration of the various phases of gene expression, including transcription, translation, and mRNA decay
A recently discovered molecular mechanism, in which subunits of RNA polymerase II (Pol II) associate to mRNAs during transcription and control their decay, could explain how such transcription-decay counter-action works. How such potential coupling responds to physiological conditions and how it shapes transcriptome kinetics remain unknown
Summary
The dynamics of the transcriptome in response to environmental changes is governed by two opposing processes – RNA production, namely transcription, and RNA degradation. Genome-wide techniques have been established that allow to measure separately the contribution of mRNA degradation [1,2,3,4] and transcription [5,6,7,8] to the balanced mRNA levels in the cell. Such studies revealed extensive regulation on both production and degradation rates. The decay rates of some genes across various growth conditions showed extensive variation, featuring stabilization in some conditions and de-stabilization in others [9,11,12]
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