R35GM145359

Mechanisms of Bacterial RNA Degradation - Project Summary

The overarching goal of this research project is to understand the basic principles that govern messenger RNA degradation, a cellular process that plays a key role in regulating gene expression in all organisms. The immediate goal is to elucidate the impact of the 5' end on bacterial mRNA lifetimes. In particular, this research will focus on understanding the influence of 5'-terminal caps and 5'-end-dependent endonucleolytic cleavage on rates of mRNA degradation in bacteria.

Long thought to reside exclusively on eukaryotic RNA transcripts, caps of various kinds have now been found on RNA 5' ends in bacteria, yet many important aspects of their function remain unexplained. In addition, the regulatory endonuclease RNase E has recently been shown to locate cleavage sites in monophosphorylated RNA by a novel scanning mechanism akin to linear diffusion from the 5' end, but how it does so is unknown.

The specific objectives of this research project are to elucidate the structural and phylogenetic diversity of bacterial mRNA capping and the interplay between capping, cell physiology, and stress. Furthermore, the project aims to determine the molecular mechanism by which RNase E scans RNA in search of cleavage sites, the influence of the cellular environment on this process, and the breadth of its regulatory impact. A combination of molecular biological, biochemical, biophysical, and genetic methods will be employed to achieve these objectives.

The knowledge gained from these studies will provide fundamental insights into novel aspects of gene regulation that have been implicated in bacterial pathogenesis and antibiotic sensitivity.

New York University

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

New York, New York 100168367 United States

Single Zip Code

Maximizing Investigators' Research Award (R35 - Clinical Trial Optional) (PAR-19-367)

Amendment Since initial award the total obligations have increased 316% from $768,282 to $3,195,479.