Myelin regulatory factor
MyRF
, also known as myelin gene regulatory factor (MRF), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

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 ...

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'' (r ...

'' and MYRFA from '' Dictyostelium''. All orthologs have a DNA-binding domain of high homology to the ''

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

'' protein Ndt80 (a p53-like transcription factor) and therefore likely act as a transcription factor.

Function

MyRF is a

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

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

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

. It is therefore of critical importance in the development and maintenance of myelin sheaths. The expression of MYRF is specific to mature, myelinating oligodendrocytes in the CNS. It has been shown to be critical for the maintenance of myelin by these cells. Following

ablation Ablation ( la, ablatio – removal) is 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, and include spacecraft materi ...

of MYRF the expression of myelin genes such as

PLP1 Proteolipid protein 1 (PLP1) is a form of myelin proteolipid protein (PLP). Mutations in ''PLP1'' are associated with Pelizaeus–Merzbacher disease. It is a 4 transmembrane domain protein which is proposed to bind other copies of itself on the e ...

, MBP,

MAG Mag, MAG or mags may refer to: Arts, entertainment and media * ''MAG'' (video game), 2010 * ''Mag'' (Slovenian magazine), 1995–2010 * '' The Mag'', a British music magazine Businesses and organisations * MacKenzie Art Gallery, in Regina, Sask ...

and

MOG Mog may refer to: Entertainment Characters * Mog (''Final Fantasy VI''), in the game * Mog (Judith Kerr), a cat in Kerr's children's books * Mog, a half-man/half-dog in the film ''Spaceballs'' * A cat in the Meg and Mog children's books by Helen ...

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 (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. This underlines the importance of an active renewal of proteins in the myelin sheath. 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 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 disease of 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 identi ...

protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. A perturbation of oligodendrocyte maturation and myelination therefore might be an underlying reason for the neurological deficits.

References

{{Transcription factors, g4 Transcription factors