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

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.