The RNA polymerase II (Pol II) is known to play a central role in transcribing all protein coding genes and non-coding RNAs (ncRNAs) in eukaryotic cells. Intriguingly, the majority of short ncRNAs are immediately degraded in the nucleus and therefore referred to as cryptic unstable transcripts (CUTs). Studies in S. cerevisiae have revealed that the Nab3-Nrd1-Sen1 (NNS) complex couples the short ncRNA transcription termination and RNA degradation by the nuclear exosome. Sen1 (252 kDa) is a well-conserved 5'→3' RNA helicase and a key player in transcription termination. In order to understand better the mechanism of termination, the helicase core domain of Sen1 (94 kDa) was expressed, purified and crystallized, and the crystal structure was solved. As shown in this work, Sen1 helicase domain has a very similar overall structure to that of Upf1-like helicases. Surprisingly, the structure reveals a unique feature, the “brace”, which fastens the accessory subdomains to RecA1 and frames the helicase in a favorable conformation for RNA binding. Moreover, structure based biochemical studies reveal that the “prong” is an essential element for 5'→3' unwinding and releasing the transcription complex from the template. Finally, I discuss the mechanism of RNA helicase translocation in the 5'→3' direction and propose a structure based model for Pol II elongation complex dissociation
