Polynucleotide Phosphorylase (PNPase) is a bifunctional

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

with a phosphorolytic 3' to 5' exoribonuclease activity and a 3'-terminal

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids ...

polymerase A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using ba ...

activity. That is, it dismantles the RNA chain starting at the 3' end and working toward the 5' end. It also synthesizes long, highly heteropolymeric tails ''in vivo''. It accounts for all of the observed residual

polyadenylation Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euk ...

in strains of ''Escherichia coli'' missing the normal polyadenylation enzyme. Discovered by Marianne Grunberg-Manago working in

Severo Ochoa Severo Ochoa de Albornoz (; 24 September 1905 – 1 November 1993) was a Spanish physician and biochemist, and winner of the 1959 Nobel Prize in Physiology or Medicine together with Arthur Kornberg for their discovery of "the mechanisms in ...

's lab in 1955, the RNA-polymerization activity of PNPase was initially believed to be responsible for DNA-dependent synthesis of messenger RNA, a notion that got disproved by the late 1950s. It is involved in mRNA processing and degradation in bacteria, plants, and animals. In humans, the enzyme is encoded by the gene. In its active form, the protein forms a ring structure consisting of three PNPase molecules. Each PNPase molecule consists of two

RNase PH RNase PH is a tRNA nucleotidyltransferase, present in archaea and bacteria, that is involved in tRNA processing. Contrary to hydrolytic enzymes, it is a phosphorolytic enzyme, meaning that it uses inorganic phosphate as a reactant to cleave nu ...

domains, an S1 RNA binding domain and a K-homology domain. The protein is present in

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

and in the

chloroplasts A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...

and

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

of some

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cells. In eukaryotes and

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...

, a structurally and evolutionary related complex exists, called the ''

exosome complex The exosome complex (or PM/Scl complex, often just called the exosome) is a multi- protein intracellular complex capable of degrading various types of RNA (ribonucleic acid) molecules. Exosome complexes are found in both eukaryotic cells and ...

''. The same abbreviation (''PNPase'') is also used for another, otherwise unrelated enzyme,

Purine nucleoside phosphorylase Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase () is an enzyme that in humans is encoded by the ''NP'' gene. It catalyzes the chemical reaction :purine nucleoside + phosphate \rightleftharpoons purine + alpha-D-ribose 1- ...

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of PNPT1 function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Pnpt1^{tm1a(KOMP)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to cr ...

program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

to determine the effects of deletion. Twenty six tests were carried out on

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

mice and two significant abnormalities were observed. No

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

embryos were identified during gestation, and therefore none survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. The remaining tests were carried out on

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. ...

mutant adult mice; no additional significant abnormalities were observed in these animals.

References

External links

* {{Portal bar, Biology, border=no Ribonucleases EC 2.7.7 Genes mutated in mice 1955 in biology