Mechanical Properties of Transcription

[摘要] Transcription is the first step in the conversion of genetic information into biological matter. It is consequently a central processes in nearly every aspect of the living world. Several decades of work has revealed stochastic and mechanical processes play a central role in transcription.Presented in this thesis is a simple mechanical description transcription making a three decade old conceptual model of transcription physical. To do this we utilize a small number of physical and mathematical ingredients generating several simple answers to many open aspects of gene expression and DNA organization.The first essential ingredient is a topological constraint which ties the helical twist of DNA and RNA polymerase to transcriptional elongation. The second ingredient balances the mechanical drag of RNA polymerase and nascent RNA against the torsional response of DNA. Additional elements incorporating the mechanical properties of the RNA polymerase are also added. These results are fundamentally important since they provide a method for characterizing previously unknown properties of transcription.The model naturally explains the phenomena of transcription bursting where fully induced genes in both in vitro as well as in vivo systems undergo periods of stalled transcriptional activity. This behavior is naturally explained in the framework developed in the thesis where transcribing RNA polymerase cause a build up of twist and mechanical energy in surrounding DNA making it harder for transcription to continue. This behavior is a compelling explanation for widespread polymerase pausing and additionally leads to an observed intrinsic, generic coupling between expression levels and fluctuations.Finally, the location and intensity of over and under twisting of DNA (calledsupercoiling) caused by transcription as well as the impact of chromatin structure on gene expression is examined. As multiple active genes and polymerase operate on a piece of shared DNA important mechanical and structural changes will occur resulting in widespread conformational changes.

[发布机构] Rice University

[效力级别] Biophysics