Protein arginine N-methyltransferase 5 is an

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. A ...

that in humans is encoded by the ''PRMT5''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events. PRMT5 is a highly conserved arginine methyltransferase that translocated from the cytoplasm to the nucleus at embryonic day ~E8.5, and during preimplantation development at the ~4-cell stage.

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 PRMT5 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 ''Prmt5^{tm2a(EUCOMM)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 crea ...

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 proper ...

to determine the effects of deletion. Twenty five 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 ...

mutant 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. Mo ...

mutant adult mice but no further abnormalities were observed. A conditional allele of Prmt5 in the mouse limb shows that it is essential for maintaining a progenitor population, as conditional mutants have limb defects

Interactions

Protein arginine methyltransferase 5 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

CLNS1A Methylosome subunit pICln is a protein that in humans is encoded by the ''CLNS1A'' gene. Interactions CLNS1A has been shown to interact with: * ITGA2B, * PRMT5, * SNRPD1, and * SNRPD3. See also * Chloride channel Chloride channels are ...

, *

Janus kinase 2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF re ...

, *

SNRPD3 Small nuclear ribonucleoprotein Sm D3 is a protein that in humans is encoded by the ''SNRPD3'' gene. Function The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splic ...

, *

SUPT5H Transcription elongation factor SPT5 is a protein that in humans is encoded by the ''SUPT5H'' gene. Interactions SUPT5H has been shown to interact with: * CDK9, * Cyclin-dependent kinase 7, * HTATSF1, * PIN1, * POLR2A, * PRMT1 and * Pr ...

, * MEP50, * RIOK1, * COPR5. PRMT5 has been shown to

with

, RIOK1 and COPR5 through an interface created by a shallow groove located on the

TIM barrel The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel, is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone. ...

domain of PRMT5 and the consensus sequence GQF /EA /Dlocated in the terminal regions of the adaptor proteins. The characterisation of the interactions occurring in the binding groove between PRMT5 and peptides derived from the adaptor proteins lead to development of protein-protein interaction (PPI) inhibitors, modulating binding between PRMT5 and the adaptor proteins. Furthermore, Asberry and co-workers synthesised the first-in-class small molecule inhibitor of the PPI between PRMT5 and MEP50. The PPI inhibitors complement a plethora of compounds directly suppressing the enzymatic activity of PRMT5.

Model organisms

Interactions

References

Further reading