Dual roles for transcription factor IIF in promoter escape by RNA polymerase II

Transcription factor (TF) IIF is a multifunctional RNA polymerase II transc ription factor that has well established roles in both transcription initia tion, where it functions as a component of the preinitiation complex and is required for formation of the open complex and synthesis of the first phos phodiester bond of nascent transcripts, and in transcription elongation, wh ere it is capable of interacting directly with the ternary elongation compl ex and stimulating the rate of transcription. In this report, we present ev idence that TFIIF is also required for efficient promoter escape by RNA pol ymerase II. Our findings argue that TFIIF performs dual roles in this proce ss. We observe (i) that TFIIF suppresses the frequency of abortive transcri ption by very early RNA polymerase II elongation intermediates by increasin g their processivity and (ii) that TFIIF cooperates with TFIIH to prevent p remature arrest of early elongation intermediates. In addition, our finding s argue that two TFIIF functional domains mediate TFIIF action in promoter escape. First, we observe that a TFIIF mutant selectively lacking elongatio n activity supports TFIIH action in promoter escape, but is defective in su ppressing the frequency of abortive transcription by very early RNA polymer ase II elongation intermediates. Second, a TFIIF mutant selectively lacking initiation activity is more active than wild type TFIIF in increasing the processivity of very early elongation intermediates, but is defective in su pporting TFIIH action in promoter escape. Taken together, our findings brin g to light a function for TFIIF in promoter escape and support a role for T FIIF elongation activity in this process.