BASIC MECHANISMS OF TRANSCRIPT ELONGATION AND ITS REGULATION

Ternary complexes of DNA-dependent RNA polymerase with its DNA templat e and nascent transcript are central intermediates in transcription. I n recent years, several unusual biochemical reactions have been discov ered that affect the progression of RNA polymerase in ternary complexe s through various transcription units. These reactions can be signaled intrinsically, by nucleic acid sequences and the RNA polymerase, or e xtrinsically, by protein or other regulatory factors. These factors ca n affect any of these processes, including promoter proximal and promo ter distal pausing in both prokaryotes and eukaryotes, and therefore p lay a central role in regulation of gene expression. In eukaryotic sys tems, at least two of these factors appear to be related to cellular t ransformation and human cancers. New models for the structure of terna ry complexes, and for the mechanism by which they move along DNA, prov ide plausible explanations for novel biochemical reactions that have b een observed. These models predict that RNA polymerase moves along DNA without the constant possibility of dissociation and consequent termi nation. A further prediction of these models is that the polymerase ca n move in a discontinuous or inchworm-like manner. Many direct predict ions of these models have been confirmed. However, one feature of RNA chain elongation not predicted by the model is that the DNA sequence c an determine whether the enzyme moves discontinuously or monotonically . In at least two cases, the encounter between the RNA polymerase and a DNA block to elongation appears to specifically induce a discontinuo us mode of synthesis. These findings provide important new insights in to the RNA chain elongation process and offer the prospect of understa nding many significant biological regulatory systems at the molecular level.