RNA polymerase (Pol) II produces mRNA during transcription of protein-coding genes in all eukaryotic cells. In my talk, I will report on the 3.4 Å-resolution cryo-EM structure of a mammalian Pol II elongation complex (EC). The structure reveals details of EC-nucleic acid interactions, and yields insights into the conformational dynamics of Pol II. Upstream DNA emanates from the active center cleft at an angle of ~105º with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5). Our results provide a structural basis for the mechanistic analysis of human transcription elongation.