RNAPII transcription is achieved through several steps, which are highly regulated and coordinated among them and with other nuclear events. A great number of factors regulate the whole process, where the levels of RNAPII phosphorylation are crucial. In addition, other kind of regulation is imposed by the architecture of the chromatin. Thus, there are actively transcribed genes that are organized into loops in which the 5' and 3' ends physically associate. In these genes, the initiation and termination complexes directly interact forming a loop that facilitates the formation of a reinitiation complex. In consequence, gene loops enhance transcription reinitiation by facilitating the delivery of RNAPII from the terminator to the promoter of the same gene. Gene looping plays important regulatory roles. For instance, it regulates termination and determines the directionality of transcription from bidirectional promoters, then avoiding small ncRNAs expression, whose upregulation might impair cell viability. Despite the large amount of knowledge on transcription and its regulation, the termination and gene looping process are still not well understood, and there is a growing number of evidences suggesting that these two processes are also fine-tuned and co-regulated. Indeed, an specific RNAPII phosphorylation code is required for proper transcription termination. RNAP II subunits involved in the initiation and elongation steps of transcription are well studied, whereas there is a modest understanding about which subunits are involved in the termination. Some preliminary studies have reported a possible role for Rpb3, Rpb11, Rpb4 and Rpb7 subunits in the termination of transcription. Nevertheless solid evidences in support of the role of these subunits in termination are still missing. We have shown that Rpb4 and 7 subunits are required to properly maintain RNAPII phosphorylation levels, and more recently our data suggest that rpb mutations affecting the integrity of Rpb4/7 heterodimer also alters CTD phosphorylation. Moreover, our results indicate that Rpb4 plays a key role in transcription termination and in the formation of gene loops in S.cerevisiae, likely by means of its interaction with preinitiation and termination factors. Next, the question to aswer will be whether these two processes, RNAPII phosphorylation and gene looping formation, are co-regulated via Rpb4.

Resumen del trabajo presentado a la II Reunión de la Red Temática de Excelencia: "The mRNA Life".

BFU2015-71978-REDT.

Peer reviewed