Myelin regulatory factor (MRF), Myelin gene regulatory factor, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Orthologs

Myelin regulatory factor is encoded by the ''Myrf/GM98'' gene in mice and by the ''MYRF'' gene in humans. The family of MyRF-like-proteins also contains the orthologues pqn-47 from ''

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' ( ...

'' and MYRFA from ''

Dictyostelium ''Dictyostelium'' is a genus of single- and multi-celled eukaryotic, phagotrophic bacterivores. Though they are Protista and in no way fungal, they traditionally are known as "slime molds". They are present in most terrestrial ecosystems a ...

''. All orthologs have a

DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...

of high homology to the ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

'' protein Ndt80 (a

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

-like

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

) and therefore likely act as a transcription factor.

Function

MyRF is a

that promotes the expression of many genes important in the production of

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

. It is therefore of critical importance in the development and maintenance of myelin sheaths. The expression of MYRF is specific to mature, myelinating

oligodendrocytes Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axon ...

in the CNS. It has been shown to be critical for the maintenance of myelin by these cells. Following

ablation Ablation ( – removal) is the removal or destruction of something from an object by vaporization, chipping, erosion, erosive processes, or by other means. Examples of ablative materials are described below, including spacecraft material for as ...

of MYRF the expression of myelin genes such as PLP1, MBP,

MAG Mag, MAG, Mags or mags may refer to: Arts, entertainment and media * ''MAG'' (video game), released in 2010 * ''Mág'' (film), a 1988 Czech film * ''Mag'' (Slovenian magazine), published from 1995 to 2010 * '' The Mag'', a British music magazin ...

and MOG drops rapidly. Therefore, MYRF is a key regulator and likely a direct activator of the expression of these genes.

Animal models

Mice that lose MYRF during adulthood present with a severe demyelination similar to that seen in animal models of

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. This underlines the importance of an active renewal of proteins in the

myelin sheath Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

. Further, the activity of MYRF increases during remyelination, suggesting it has a critical role in this process. Animals with repressed Myrf in a proportion of

oligodendrocyte Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axons ...

precursor cells showed a delayed functional recovery from spinal cord injury. Myrf has been shown to be significantly downregulated in a mouse model carrying the same mutation in the

NPC1 Niemann-Pick disease, type C1 (NPC1) is a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the ''NPC1'' gene (chromosome location 18q11). Function ''NPC1'' was identified as ...

protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. Therefore, a disruption of oligodendrocyte formation and myelination may be the root cause of the neurological abnormalities.

References

{{Transcription factors, g4 Transcription factors