RNA polymerase (Pol) II catalyses DNA-dependent RNA synthesis during gene 
transcription. There is, however, evidence that Pol II also possesses 
RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA 
template, can extend RNA by several nucleotides in the absence of DNA, and has 
been implicated in the replication of the RNA genomes of hepatitis delta virus 
(HDV) and plant viroids. Here we show the intrinsic RdRP activity of Pol II with 
only pure polymerase, an RNA template-product scaffold and nucleoside 
triphosphates (NTPs). Crystallography reveals the template-product duplex in the 
site occupied by the DNA-RNA hybrid during transcription. RdRP activity resides 
at the active site used during transcription, but it is slower and less 
processive than DNA-dependent activity. RdRP activity is also obtained with part 
of the HDV antigenome. The complex of transcription factor IIS (TFIIS) with Pol 
II can cleave one HDV strand, create a reactive stem-loop in the hybrid site, 
and extend the new RNA 3' end. Short RNA stem-loops with a 5' extension suffice 
for activity, but their growth to a critical length apparently impairs 
processivity. The RdRP activity of Pol II provides a missing link in molecular 
evolution, because it suggests that Pol II evolved from an ancient replicase 
that duplicated RNA genomes.