Intrinsic transcription termination plays a crucial role in regulating gene
expression in prokaryotes. After a short pause, the termination signal app
ears in RNA as a hairpin that destabilizes the elongation complex (EC). We
demonstrate that negative and positive-termination factors control the effi
ciency of termination primarily through a direct modulation of hairpin fold
ing and, to a much lesser extent, by changing pausing at the point of termi
nation. The mechanism controlling hairpin formation at the termination poin
t relies on weak protein interactions with single-stranded RNA, which corre
sponds to the upstream portion of the hairpin. Escherichia coli NusA protei
n destabilizes these interactions and thus promotes hairpin folding and ter
mination. Stabilization of these contacts by phage lambda N protein leads t
o antitermination.