Polynucleotide phosphorylase: an evolutionary conserved gene with an expanding repertoire of functions

RNA metabolism plays a seminal role in regulating diverse physiological processes. Polynucleotide phosphorylase (PNPase) is an evolutionary conserved 3',5' exoribonuclease, which plays a central role in RNA processing in bacteria and plants. Human polynucleotide phosphorylase (hPNPase old-35) was cloned using an inventive strategy designed to identify genes regulating the fundamental physiological processes of differentiation and senescence. Although hPNPase old-35 structurally and biochemically resembles PNPase of other species, targeted overexpression and inhibition studies reveal that hPNPase old-35 has evolved to serve more specialized functions in humans. The present review provides a global perspective on the structure and function of PNPase and then focuses on hPNPase old-35 in the contexts of differentiation and senescence.