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Trends Biochem Sci. 2016 Apr;41(4):293-310. doi: 10.1016/j.tibs.2015.12.009. Epub 2016 Jan 25.

A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure.

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Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Electronic address:
Departments of Biochemistry and Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:


The vectorial (5'-to-3' at varying velocity) synthesis of RNA by cellular RNA polymerases (RNAPs) creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived, pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here, we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNAP and nascent RNA structure. We categorize and rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies.


RNA polymerase; RNA processing; RNA structure; termination and antitermination; transcriptional pausing

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