RNA Polymerase II Subunits Link Transcription and mRNA Decay to Translation

Abstract

Little is known about crosstalk between the eukaryotic transcription and translation machineries that operate in different cell compartments. The yeast proteins Rpb4p and Rpb7p represent one such link as they form a heterodimer that shuttles between the nucleus, where it functions in transcription, and the cytoplasm, where it functions in the major mRNA decay pathways. Here we show that the Rpb4/7 heterodimer interacts physically and functionally with components of the translation initiation factor 3 (eIF3), and is required for efficient translation initiation. Efficient translation in the cytoplasm depends on association of Rpb4/7 with RNA polymerase II (Pol II) in the nucleus, leading to a model in which Pol II remotely controls translation. Hence, like in prokaryotes, the eukaryotic translation is coupled to transcription. We propose that Rpb4/7, through its interactions at each step in the mRNA lifecycle, represents a class of factors, "mRNA coordinators," which integrate the various stages of gene expression into a system.

Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation

“…There is also evidence that nuclear and cytoplasmic mRNA metabolism are linked. The Pol II subcomplex Rpb4/7 shuttles between the nucleus and cytoplasm (Selitrennik et al 2006) and is involved in transcription (Edwards et al 1991) and mRNA translation and degradation (Lotan et al 2005;Lotan et al 2007;Harel-Sharvit et al 2010). The Ccr4-Not complex is involved in mRNA degradation (Tucker et al 2002) and also in transcription (Liu et al 1998;Collart 2003;Collart and Timmers 2004;Kruk et al 2011).…”

“…The mRNA is then decapped and degraded by exonucleases from both ends. Despite the spatial separation of mRNA synthesis and translation/degradation, there is evidence that these processes are coordinated (Lotan et al 2005;Lotan et al 2007;Harel-Sharvit et al 2010).…”

The AMP-activated Protein Kinase Snf1 Regulates Transcription Factor Binding, RNA Polymerase II Activity, and mRNA Stability of Glucose-repressed Genes in Saccharomyces cerevisiae

“…The same group reported that cytoplasmic mRNA decay is accelerated by association with a subcomplex of RNA pol II. This subcomplex, Rpb4/7, shuttles with mRNAs between the nucleus and cytoplasm, thus apparently linking transcription with mRNA stability (65)(66)(67)(68). Another study reported that glucose sensing involves coordinated transcriptional repression and mRNA decay (69).…”

Growth rate controls mRNA turnover in steady and non-steady states

“…22,23 Another regulatory connection between transcription and mRNA decay, but in the direction from nucleus (transcription) to cytoplasm, has also been established since mRNAs can be co-transcriptionally bound by factors that imprint them and influence their stability and translatability. 24,25 The disruption of the mechanistic coupling between transcription and mRNA degradation helps to explain the regulation of the mRNAs that do change with growth (Fig. 1B).…”