External guide sequence technology: a path to development of novel antimicrobial therapeutics

CAROL DAVIES SALA; ALFONSO SOLER-BISTUE; ROBERT A. BONOMO; ANGELES ZORREGUIETA; MARCELO E. TOLMASKY

ANN. N. Y. ACADEMY SCIEN.

New York Academy of Sciences

Año: 2015

1749-6632

RNase P is a ribozyme originally identified for its role in maturation of tRNAs by cleavage of precursor tRNAs(pre-tRNAs) at the 5-end termini. RNase P is a ribonucleoprotein consisting of a catalytic RNA molecule and,depending on the organism, one or more cofactor proteins. The site of cleavage of a pre-tRNA is identified byits tertiary structure; and any RNA molecule can be cleaved by RNase P as long as the RNA forms a duplex thatresembles the regional structure in the pre-tRNA. When the antisense sequence that forms the duplex with the strandthat is subsequently cleaved by RNase P is in a separate molecule, it is called an external guide sequence (EGS).These fundamental observations are the basis for EGS technology, which consists of inhibiting gene expression byutilizing an EGS that elicits RNase P?mediated cleavage of a target mRNA molecule. EGS technology has been usedto inhibit expression of a wide variety of genes, and may help development of novel treatments of diseases, includingmultidrug-resistant bacterial and viral infections.