In Science this week, a team led by Stanford University researchers report the architecture of a complete, 32-protein, RNA polymerase II transcription pre-initiation complex. The structure was determined using cryo-EM and a combination of chemical cross-linking and mass spectrometry, and showed a "marked division" in two parts — one containing all the general transcription factors and the other pol II. Promoter DNA was found to associate only with the general transcription factors, suspended above the pol II cleft and not in contact with pol II, underlying its "conversion to a transcriptionally active state," with the pre-initiation complex poised for the formation of a transcription bubble and descent of the DNA into the pol II cleft.
Also in the online early edition of Science this week, researchers from Harvard University report that the codons at the N-terminuses of genes affect the expression of those genes. Using more than 14,000 synthetic reporters in Escherichia coli, the investigators determined that placing rare codons at N-terminuses increases expression by about 14-fold, as compared to common codons. Decreased GC content, they note, particularly increased expression. "Natural genomic sequence is often not suited to distinguish between conflicting hypotheses of how sequence affects function; multiplexed assays of large synthetic DNA libraries provide a powerful method to examine such hypotheses in a controlled manner," the researchers add.