Sub1, two domains, two functions: transcription initiation versus elongation

PAULA ALLEPUZ, ALEJANDRO COLLIN; JAIME ALEGRIO LOURO; CARLOS FERNÁNDEZ-TORNERO; OLGA CALVO

Saint Felieu

Congreso; Embo transcription meeting 2014-Sant Felieu; 2014

EMBO

The transcriptional coactivator Sub1 has been implicated in several steps of mRNA metabolism in yeast, such as the activation of transcription, termination and 3?-end formation [1]. Most recently it has been shown that it is a functional component of the preinitiation complex [2]. Additionally, we have shown that Sub1 globally regulates RNA polymerase II phosphorylation [3] and promotes transcription elongation [4].Sub1 was originally described as a transcriptional stimulatory protein based on its homology to human positive coactivator PC4 and its capacity to bind the general transcription factor TFIIB. Both are ssDNA binding proteins and have been implicated in DNA-dependent processes other than transcription, such as DNA repair and replication [1]. Although Sub1 shows strong similarity to PC4, in particular at the level of their DNA binding domains, Sub1 it is much larger. Specifically, it has an extra C-terminal domain with an unknown function, suggesting that Sub1 might have functional differences due to this additional domain.We have performed a detailed analysis of the ssDNA binding and C-terminal domains and identified the essential residues involved in Sub1 DNA binding capacity, which are not required during transcription elongation. Additionally, our data indicates that the C-terminus domain of Sub1, the function of which was previously unknown, might be important in promoting Sub1 release from the promoter to facilitate transcription elongation. In summary, Sub1 plays a dual function during transcription, being a pre-initiation factor via its DNA binding domain, and a transcription elongation factor through its C-terminus domain.