Transcription factors TFIIF, ELL, and elongin negatively regulate SII-induced nascent transcript cleavage by non-arrested RNA polymerase II elongation intermediates

TFIIF, ELL, and Elongin belong to a class of RNA polymerase II transcriptio n factors that function similarly to activate the rate of elongation by sup pressing transient pausing by polymerase at many sites along DNA templates, SII is a functionally distinct RNA polymerase II elongation factor that pr omotes elongation by reactivating arrested polymerase, Studies of the mecha nism of SII action have shown (i) that arrest of RNA polymerase II results from irreversible displacement of the 3'-end of the nascent transcript from the polymerase catalytic site and (ii) that SII reactivates arrested polym erase by inducing endonucleolytic cleavage of the nascent transcript by the polymerase catalytic site thereby creating a new transcript 3'-end that is properly aligned with the catalytic site and can be extended. SII also ind uces nascent transcript cleavage by paused but non-arrested RNA polymerase H elongation intermediates, leading to the proposal that pausing may result from reversible displacement of the 3'-end of nascent transcripts from the polymerase catalytic site. On the basis of evidence consistent with the mo del that TFIIF, ELL, and Elongin suppress pausing by preventing displacemen t of the 3'-end of the nascent transcript from the polymerase catalytic sit e, we investigated the possibility of cross-talk between SII and transcript ion factors TFIIF, ELL, and Elongin, These studies led to the discovery tha t TFIIF, ELL, and Elongin are all capable of inhibiting SII-induced nascent transcript cleavage by non-arrested RNA polymerase II elongation intermedi ates, Here we present these findings, which bring to light a novel activity associated with TFIIF, ELL, and Elongin and suggest that these transcripti on factors may expedite elongation not only by increasing the forward rate of nucleotide addition by RNA polymerase II, but also by inhibiting SII-ind uced nascent transcript cleavage by non-arrested RNA polymerase II elongati on intermediates.