The identified as a 783-amino-acid exoribonuclease upregulated gene during

The import of selected macromolecules encoded by
the nuclear genome is critical for the proper function of mammalian
mitochondria. In contrast with protein import machinery in mitochondria, little
known regarding RNA import pathways that is crucial for proper replication and
transcription of mitochondria genome. Diverse mechanisms has been proposed for
the importing of nucleus-encoded RNA into the mitochondrial, with one of the
recent one being the involvement of PNPase for importing of small structured
RNAs including RNase P RNA, MRP RNA, and 5S rRNA. Consistent with the
importance of this process, PNPase dysfunction though mutations in the
corresponding gene has been shown to cause variety of human diseases
characterized by respiratory-chain deficiency, hearing loss and sever
multisystem disease.

Polynucleotide phosphorylase (PNPase) is an
evolutionary conserved 3′-5′ exoribonuclease that uses the phosphorolytic
mechanism to digest RNA and also can function as a template dependent RNA
polymerase. The encoding gene for hPNPase (PNPT1) was first identified as a
783-amino-acid exoribonuclease upregulated gene during cellular senescence and
terminal differentiation through its RNA-degrading function in the cytosol. Moreover,
PNPase can have a potential role in compacting viral infections in mammalian
cells. In human cells PNPase is expressed ubiquitously in normal tissues and it
can be further induced by type I int­­erferons in order to degraded c-myc mRNA
that are involved in a wide range of cellular process including
differentiation, proliferation, and tumorgenesis.

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PNPase from different
species having similar domain structures that consist of 5 domains. Two
catalytic RNase PH domains that are connected by a unique ?-helical domain
followed by K Homology (KH) and S1 domains at the C-terminus. Previously solved
crystal structures of bacterial and human PNPase show a conserved trimeric doughnut-shaped
architecture with a central channel to dock single stranded RNA into the enzyme’s
catalytic sites. The current model for PNPase degradation activity is based on
the available structures and mutations in which indicating the importance of S1
domain in RNA binding, KH domain for RNA binding as well as supporting the
trimeric structure. Specifically, KH domain contains GXXG motif that has been
shown to play an important role in RNA binding not only in PNPase also other
proteins containing KH domain.