Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterase PDE12 is a medically important esterase-family member that hydrolyzes 2'-5'-linked oligoadenylates (2-5A), which are involved in the regulation of biological processes related to the antiviral and antitumour activity that can be induced by interferons. Here, cloning, purification and crystallization of the C-terminal endonuclease/exonuclease/phosphatase-homology domain of human PDE12 is reported. The crystals belonged to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 111.3, c = 192.4 A, and diffracted to 2.5 A resolution. Assuming the presence of three molecules in the asymmetric unit, the solvent content was estimated to be about 44.0%.
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PMID:Crystallization and preliminary X-ray crystallographic analysis of human phosphodiesterase 12. 2044 49

The vertebrate 2-5A system is part of the innate immune system and central to cellular antiviral defense. Upon activation by viral double-stranded RNA, 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are synthesized by one of several 2'-5'-oligoadenylate synthetases. These unusual oligonucleotides activate RNase L, an unspecific endoribonuclease that mediates viral and cellular RNA breakdown. Subsequently, the 2-5As are removed by a 2'-phosphodiesterase (2'-PDE), an enzyme that apart from breaking 2'-5' bonds also degrades regular, 3'-5'-linked oligoadenylates. Interestingly, 2'-PDE shares both functionally and structurally characteristics with the CCR4-type exonuclease-endonuclease-phosphatase family of deadenylases. Here we show that 2'-PDE locates to the mitochondrial matrix of human cells, and comprise an active 3'-5' exoribonuclease exhibiting a preference for oligo-adenosine RNA like canonical cytoplasmic deadenylases. Furthermore, we document a marked negative association between 2'-PDE and mitochondrial mRNA levels following siRNA-directed knockdown and plasmid-mediated overexpression, respectively. The results indicate that 2'-PDE, apart from playing a role in the cellular immune system, may also function in mitochondrial RNA turnover.
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PMID:Human 2'-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover. 2124 38

Transcription of the mitochondrial genome results in polycistronic precursors, which are processed mainly by the release of tRNAs interspersed between rRNAs and mRNAs. In many metazoan mitochondrial genomes some tRNA genes overlap with downstream genes; in the case of human mitochondria the genes for tRNA(Tyr) and tRNA(Cys) overlap by one nucleotide. It has previously been shown that processing of the common precursor releases an incomplete tRNA(Tyr) lacking the 3'-adenosine. The 3'-terminal adenosine has to be added before addition of the CCA end and subsequent aminoacylation. We show that the mitochondrial poly(A) polymerase (mtPAP) is responsible for this A addition. In vitro, a tRNA(Tyr) lacking the discriminator is a substrate for mtPAP. In vivo, an altered mtPAP protein level affected tRNA(Tyr) maturation, as shown by sequencing the 3' ends of mitochondrial tRNAs. Complete repair could be reconstituted in vitro with three enzymes: mtPAP frequently added more than one A to the 3' end of the truncated tRNA, and either the mitochondrial deadenylase PDE12 or the endonuclease RNase Z trimmed the oligo(A) tail to a single A before CCA addition. An enzyme machinery that evolved primarily for other purposes thus allows to tolerate the frequent evolutionary occurrence of gene overlaps.
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PMID:Mitochondrial poly(A) polymerase is involved in tRNA repair. 2635 63