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 鈥榦verlapping pathway screening鈥?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, hPNPase ~(old-35 ) modulates gene expression that in turn has 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.