Towards molecular systems biology of gene transcription and regulation

Abstract

Ten years after the determination of the RNA polymerase II structure, the basic mechanism of mRNA synthesis during gene transcription is known. In the future, the initiation and regulation of transcription must be studied with a combination of structural biology, biochemistry, functional genomics, and computational methods. In this article, the efforts of our laboratory to move from an integrated structural biology of gene transcription towards molecular systems biology of gene regulation are reviewed.

Basic mechanism of transcription by RNA polymerase II

“…Although it might appear that “the basic mechanism of mRNA synthesis during gene transcription is known” from the structural point of view 107 , from the studies reviewed herein one can see that the same crystallographic models of RNAPII can be consistent with a number of dramatically different reaction mechanisms, which then have to be ranked kinetically and thermodynamically using complementary methods, such as MD and TI 97 . In fact, many transcription “mechanisms” proposed to date amount to little more than nominative narratives, enumerating the actual or the conjectural steps of a pathway with no regard to physical parameters (such as potential energy surface, activation barrier, initial velocity for molecular collisions, etc.)…”