Regulation of transcription elongation is an important mechanism in controlling 
eukaryotic gene expression. SII is an RNA polymerase II-binding protein that 
stimulates transcription elongation and also activates nascent transcript 
cleavage by RNA polymerase II in elongation complexes in vitro (Reines, D. 
(1992) J. Biol. Chem. 267, 3795-3800). Here we show that SII-dependent in vitro 
transcription through an arrest site in a human gene is preceded by nascent 
transcript cleavage. RNA cleavage appeared to be an obligatory step in the SII 
activation process. Recombinant SII activated cleavage while a truncated 
derivative lacking polymerase binding activity did not. Cleavage was not 
restricted to an elongation complex arrested at this particular site, showing 
that nascent RNA hydrolysis is a general property of RNA polymerase II 
elongation complexes. These data support a model whereby SII stimulates 
elongation via a ribonuclease activity of the elongation complex.