RoXaN also known as ZC3H7B (zinc finger CCCH-type containing 7B), is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the ZC3H7B gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. RoXaN is a protein that contains tetratricopeptide repeat

Tetratricopeptide

The tetratricopeptide repeat is a structural motif. It consists in a degenerate 34 amino acid sequence motif identified in a wide variety of proteins. It is found in tandem arrays of 3–16 motifs, which form scaffolds to mediate protein–protein interactions and often the assembly of multiprotein...

 and leucine-aspartate repeat as well as zinc finger

Zinc finger

Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...

 domains. This protein also interacts with the rotavirus

Rotavirus

Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...

 non-structural protein NSP3

NSP3 (rotavirus)

Rotavirus protein NSP3 is bound to the 3' end consensus sequence of viral mRNAs in infected cells.Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3: using short oligoribonucleotides, it was established that the minimal RNA sequence required...

.

Function

Rotavirus

Rotavirus

Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...

 mRNAs are capped

5' cap

The 5' cap is a specially altered nucleotide on the 5' end of precursor messenger RNA and some other primary RNA transcripts as found in eukaryotes. The process of 5' capping is vital to creating mature messenger RNA, which is then able to undergo translation...

 but not polyadenylated

Polyadenylation

Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...

, and viral proteins are translated

Rotavirus translation

Rotavirus translation, the process of translating mRNA into proteins, occurs in a different way in Rotaviruses. Unlike the vast majority of cellular proteins in other organisms, in Rotaviruses the proteins are translated from capped but nonpolyadenylated mRNAs...

 by the cellular translation machinery. This is accomplished through the action of the viral nonstructural protein

Nonstructural protein

In virology, a nonstructural protein is a protein encoded by a virus but it is not part of the viral particle....

 NSP3

NSP3 (rotavirus)

Rotavirus protein NSP3 is bound to the 3' end consensus sequence of viral mRNAs in infected cells.Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3: using short oligoribonucleotides, it was established that the minimal RNA sequence required...

 which specifically binds the 3' consensus sequence of viral mRNAs and interacts

Rotavirus translation

Rotavirus translation, the process of translating mRNA into proteins, occurs in a different way in Rotaviruses. Unlike the vast majority of cellular proteins in other organisms, in Rotaviruses the proteins are translated from capped but nonpolyadenylated mRNAs...

 with the eukaryotic translation initiation factor eIF4G

Eukaryotic initiation factor

Eukaryotic initiation factors are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitation complex , recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA,...

 I.

RoXaN (rotavirus X protein associated with NSP3

NSP3 (rotavirus)

Rotavirus protein NSP3 is bound to the 3' end consensus sequence of viral mRNAs in infected cells.Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3: using short oligoribonucleotides, it was established that the minimal RNA sequence required...

) is 110-kDa cellular protein that contains a minimum of three regions predicted to be involved in protein-protein or nucleic acid-protein interactions. A tetratricopeptide

Tetratricopeptide

The tetratricopeptide repeat is a structural motif. It consists in a degenerate 34 amino acid sequence motif identified in a wide variety of proteins. It is found in tandem arrays of 3–16 motifs, which form scaffolds to mediate protein–protein interactions and often the assembly of multiprotein...

 repeat region, a protein-protein interaction domain most often found in multiprotein complexes, is present in the amino-terminal region. In the carboxy terminus, at least five zinc finger

Zinc finger

Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...

 motifs are observed, further suggesting the capacity of RoXaN to bind other proteins or nucleic acids. Between these two regions exists a paxillin

Paxillin

Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge and should not be confused with the neurotoxin paxilline. The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions, it is presumed through a direct...

 leucine-aspartate repeat (LD) motif which is involved in protein-protein interactions.

Clinical signficance

RoXaN is capable of interacting with NSP3 in vivo and during rotavirus infection. Domains of interaction correspond to the dimerization domain of NSP3 (amino acids 163 to 237) and the LD domain of RoXaN (amino acids 244 to 341). The interaction between NSP3 and RoXaN does not impair the interaction between NSP3 and eIF4G I, and a ternary complex made of NSP3, RoXaN, and eIF4G I can be detected in rotavirus-infected cells, implicating RoXaN in translation

Rotavirus translation

Rotavirus translation, the process of translating mRNA into proteins, occurs in a different way in Rotaviruses. Unlike the vast majority of cellular proteins in other organisms, in Rotaviruses the proteins are translated from capped but nonpolyadenylated mRNAs...

 regulation.

Expression of RoXaN was found to be correlated with a higher tumor grad in GIST (gastrointestinal stromal tumor

Gastrointestinal stromal tumor

A gastrointestinal stromal tumor is one of the most common mesenchymal tumors of the gastrointestinal tract...

s).

Further reading