Domain acquisition enabled functional expansion of the TFIIS transcription factor family.

TFIIS and its homologs were long considered a delimited family of transcription factors, for the ability to induce RNA Polymerase II backtracking and nascent RNA cleavage. Recent studies however show that the relevant domains, which correspond to the TFIIS middle and carboxyterminal regions, are used to control transcription by additional protein architectures. The TFIIS middle region is paired with a SPOC domain in BYE1, the founder protein of the subfamily, and in its homologs; this combination of domains accommodates additional features such as a small zinc finger resembling the TFIIS carboxyterminal region. In metazoans, the architecture has evolved additional extensions to act on downstream RNA processing. Here, we argue in favor of a single protein superfamily encompassing TFIIS, BYE1, and their metazoan homologs. We conclude that the TFIIS middle domain comprises a common Pol2-interacting domain, shared by various generic protein functions. Domain composition of the vertebrate BYE1 homologs indicates a role in transcription elongation. Depending on the combination with other structures, the TFIIS middle domain may promote mutually exclusive activities, for example backtracking versus RNA synthesis and splicing. In this way, exchange of TFIIS for other superfamily members supports the separate Pol2 actions.