Their findings were published online April 16 in an article, “A Role for REP Sequences in Regulating Translation,” in the academic journal Molecular Cell.
“This work was a continuation of our studies to understand the totality of RNA metabolism in cells,” said Murray P. Deutscher, Ph.D., professor of biochemistry and molecular biology and corresponding author of the journal article. “During the course of this work, we discovered that structures called REP [repetitive extragenic palindromic] sequences that are found downstream of many genes, and whose function has been uncertain, actually can regulate expression of their upstream genes.”
Deutscher’s principal co-investigator was Kenneth E. Rudd, Ph.D., associate professor of biochemistry and molecular biology, whose research has, for more than two decades, included mapping, cataloging and functional analysis of the E. coli REP elements.
“One of the important things we learned is that hundreds of genes in E. coli, and almost certainly in closely related bacteria such as Salmoa that also have REP elements, are subject to a new mode of control of gene expression,” said Rudd. “This occurs at a location that had not been previously considered a site for regulation of gene expression, the part of the mRNA that comes after the gene’s coding sequence. This is meaningful, in part, because it helps us understand more completely how bacteria respond to their environment. It also gives us a new way to manipulate gene expression.”
Gene expression underlies everything that goes on in cells, said Deutscher.
“This work helps to understand how cells work and regulate expression of their gene products,” he said. “This is necessary information to have before one can hope to understand what goes wrong in disease states.”
Rudd said the findings have no obvious immediate medical application.
“However,” he said, “the presence of REP elements in many related pathogenic enteric bacteria means it is feasible this discovery could be part of an intervention strategy someday.”
Their work has opened up new avenues of biochemistry and bioinformatics research to further study the mechanistic and regulatory aspects of REP-mediated arrest of translation in these pathogens in more detail, said Rudd.
The two scientists are now collaborating on an NIH grant proposal to continue their investigations. They hope to gain a better understanding of what is special about the genes regulated by this mechanism, and what the physiological consequences to the cell are if it is interrupted.
The paper’s first author, Wenxing Liang, Ph.D., a former post-doctoral student, has since left the Miller School for a position at Qingdao Agricultural University in China.
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