Abstract
Human polynucleotide phosphorylase (hPNPaseold-35) is an evolutionary conserved RNA-processing enzyme with expanding roles in regulating cellular physiology. hPNPaseold-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 hPNPaseold-35 structurally and biochemically resembles PNPase of other species, overexpression and inhibition studies reveal that hPNPaseold-35 has evolved to serve more specialized and diversified functions in humans. Targeting specific mRNA or non-coding small microRNA, hPNPaseold-35 modulates gene expression that in turn has a pivotal role in regulating normal physiological and pathological processes. In these contexts, targeted overexpression of hPNPaseold-35 represents a novel strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions.
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Acknowledgements
This study was supported in part by NIH grants R01 CA097318, R01 CA127641, CA134721, and P01 CA104177, the Samuel Waxman Cancer Research Foundation and the National Foundation for Cancer Research (PBF) and NIH grant R01 CA134721 (DS). DS is the Harrison Endowed Scholar in Cancer Research. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research and is a SWCRF Investigator.
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Das, S., Bhutia, S., Sokhi, U. et al. Human polynucleotide phosphorylase (hPNPaseold-35): an evolutionary conserved gene with an expanding repertoire of RNA degradation functions. Oncogene 30, 1733–1743 (2011). https://doi.org/10.1038/onc.2010.572
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DOI: https://doi.org/10.1038/onc.2010.572
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