RNA polymerase II phosphorylation and gene looping: new roles for the Rpb4/7 heterodimer in regulating gene expression

In eukaryotes, cellular RNAs are produced by three nuclear RNA polymerases (RNAPI, II, and III), which are multisubunit complexes. They share structural and functional features, although they are specialized in the synthesis of specific RNAs. RNAPII transcribes the vast majority of cellular RNAs, including mRNAs and a large number of noncoding RNAs. The structure of RNAPII is highly conserved in all eukaryotes, consisting of 12 subunits (Rpb1-12) organized into five structural modules, among which the Rpb4 and Rpb7 subunits form the stalk. Early studies suggested an accessory role for Rpb4, because is required for specific gene transcription pathways. Far from this initial hypothesis, it is now well established that the Rpb4/7 heterodimer plays much wider roles in gene expression regulation. It participates in nuclear and cytosolic processes ranging from transcription to translation and mRNA degradation in a cyclical process. For this reason, Rpb4/7 is considered a coordinator of gene expression. New functions have been added to the list of stalk functions during transcription, which will be reviewed herein: first, a role in the maintenance of proper RNAPII phosphorylation levels, and second, a role in the establishment of a looped gene architecture in actively transcribed genes.