Human Polynucleotide Phosphorylase (hPNPaseold-35): An evolutionary conserved gene with an expanding repertoire of RNA degradation functions

摘要

Human polynucleotide phosphorylase (hPNPase^old-35) is an evolutionary conserved RNA processing enzyme with expanding roles in regulating cellular physiology. hPNPase^old-35 was cloned using an innovative “overlapping pathway screening” strategy designed to identify genes coordinately regulated during the processes of cellular differentiation and senescence. Although hPNPase^old-35 structurally and biochemically resembles PNPase of other species, overexpression and inhibition studies reveal that hPNPase^old-35 has evolved to serve more specialized and diversified functions in humans. Targeting specific mRNA or non-coding small microRNA (miRNA), hPNPase^old-35 modulates gene expression that in turn plays a pivotal role in regulating normal physiological and pathological processes. In these contexts, targeted overexpression of hPNPase^old-35 represents a novel strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions.