New York University School of Medicine
Host: John Hunt
Title: 5′-terminal control of mRNA degradation
Abstract: Messenger RNA degradation plays a pivotal role in the control of gene expression in all realms of life, but the mechanisms that govern the distinct half-lives of mRNAs are poorly understood. For example, the diversity of mRNA lifetimes in bacterial cells is difficult to reconcile with the relaxed cleavage-site specificity of RNase E, a regulatory endonuclease that is crucial for controlling mRNA degradation. Mounting evidence indicates that, in E. coli, rates of mRNA decay are determined not by the number or intrinsic quality of internal cleavage sites but rather by the ease with which RNase E can gain access to them. We have discovered that a major determinant of access is the phosphorylation state of the RNA 5′ terminus, where conversion from a triphosphate to a monophosphate potentiates RNase E attack by enabling the endonuclease to bind there. It then appears to search for cleavage sites by a novel mechanism involving linear diffusion from the 5′ end along RNA segments that are single-stranded. As a consequence, the rate of cleavage at those internal sites is governed not only by the susceptibility of the 5′ terminus to phosphate removal and RNase E binding but also by any obstacles that RNase E may encounter as it scans downstream.