Gene expression is a complex phenomenon that depends on multiple protein complexes, including RNA polymerases (RNA pols). In eukaryotes, bacteria, and archaea, RNA pols are heteromultimeric complexes which, in collaboration with a large set of proteins, constitute transcriptional machineries [1],[2]. RNA pol II, which transcribes mRNAs and several noncoding RNAs, comprises 12 subunits organized in a 10-subunit core, and the heterodimer Rpb4 and Rpb7 (Rpb4/7)[3],[4]. Rpb4 and Rpb7 are indispensable for cell survival in eukaryotes [5],[6],[7],[8],[9],[10],[11]. However, in Saccharomyces cerevisiae, Rpb4 is dispensable under permissive conditions [12],[13],[14],[15],[16],[17], but is essential together with Rpb7 in stress tolerance [6]. Interestingly, RPB7 overexpression overcomes the lethality of mutant rpb4Δ under some stress conditions [18]. Rpb4 and Rpb7 show substoichiometric levels compared to other RNA pol II subunits in S. cerevisiae [19], which could be related to the dissociation of the heterodimer from the 10-subunit core complex observed only in S. cerevisiae [15],[16],[20],[21],[22]. As only~ 20% of RNA pol II complexes contain Rpb4/7 in proliferating cells [22], it has been proposed that this interaction might occur only in some transcription steps [22]. However, we speculate that dissociation may be restricted to a specific set of genes.

Rpb4 assembles with RNA pol II in the cytoplasm before the enzyme translocates to the nucleus, a process that requires the action of Rtr1 [23]. Furthermore, Rpb4/7 shuttles between the nucleus and the cytoplasm to play different roles in transcription, mRNA export, mRNA degradation and translation [16],[21],[24],[25],[26],[27],[28]. Notably, Rpb4/7 cotranscriptionally imprints mRNAs to participate in mRNA homeostasis [25],[26],[27],[28],[29],[30],[31],[32]. In line with other authors [25],[26],[27],[30],[31],[32],[33],[34],[35],[36], we speculate that Rpb4/7 is a central element of RNA pol II, and serves to coordinate transcription in the nucleus and mRNA decay in the cytoplasm.