Research in the Landick Lab

We study how RNA chain elongation by RNA polymerase (RNAP) is regulated. We use a variety of approaches to study both bacterial and human RNAPs. This diversity of methods and experimental systems is grounded in the scientific philosophy that greatest progress will be achieved by combining results from different methods and the richest intellectual insight lies in comparing evolutionarily diverse organisms. To that end, we are engaged in the following projects.

Projects

Response of bacterial RNA polymerase to intrinsic regulatory signals

Structure of elongating and paused transcription complexes

Transcription elongation factors in bacteria

Human RNA polymerase II intrinsic regulatory signals – the HIV-1 pause signal

Transcription by single RNA polymerase molecules

Novel RNA polymerase inhibitors - discovery of new antibiotics

Comparative studies of bacterial RNA polymerases

Response of bacterial RNA polymerase to intrinsic regulatory signals

RNAPs respond to intrinsic signals in DNA and RNA that cause the enyzmes to pause, arrest, or terminate RNA synthesis. Many regulatory molecules function by overriding or enhancing these intrinsic signals. To understand the fundamental mechanisms of these intrinsic signals, we dissected pause signals because they (i) play key roles in gene regulation by synchronizing movements of RNAP on genes with binding of regulatory factors to RNAP and nascent RNA (1, 2), (iii) couple transcription and translation in bacteria (1), (iii) facilitate proper RNA folding (3), and (iv) are precursors to arrest and termination. We found that pause signals come it at least two classes, those stabilized by RNA hairpins and those stabilized by backtracking of RNAP on the RNA and DNA (4). Both classes appear to be generated from a common unactivated intermediate that arises by a rearrangement in RNAP’s active site.