Elongation factor SII (also known as TFIIS) is an RNA polymerase II binding 
protein that allows bypass of template arrest sites by activating a nascent RNA 
cleavage reaction. Here we show that SII contacts the 3'-end of nascent RNA 
within an RNA polymerase II elongation complex as detected by photoaffinity 
labeling. Photocross-linking was dependent upon the presence of SII, 
incorporation of 4-thio-UMP into RNA, and irradiation and was sensitive to 
treatment by RNase and proteinase. A transcriptionally active mutant of SII 
lacking the first 130 amino acids was also cross-linked to the nascent RNA, but 
SII from Saccharomyces cerevisiae, which is inactive in concert with mammalian 
RNA polymerase II, failed to become photoaffinity labeled. SII-RNA contact was 
not detected after a labeled oligoribonucleotide was released from the complex 
by nascent RNA cleavage, demonstrating that this interaction takes place between 
elongation complex-associated but not free RNA. This shows that the 3'-end of 
RNA is near the SII binding site on RNA polymerase II and suggests that SII may 
activate the intrinsic RNA hydrolysis activity by positioning the transcript in 
the enzyme's active site.