Cytoplasmic FMR1-interacting protein 2 is a protein that in humans is encoded by the CYFIP2gene.[1][2] Cytoplasmic FMR1 interacting protein is a 1253 amino acid long protein and is highly conserved sharing 99% sequence identity to the mouse protein.[1][3] It is expressed mainly in brain tissues, white blood cells and the kidney.[4]
CYFIP2 has been shown to interact with FMR1.[1][5] CYFIP2 is a p-53 inducible protein[6] and also interacts with the Fragile=X mental retardation protein.[7]
RNA editing
The pre-mRNA of this protein is subject to RNA editing.[8] The editing site was previously recorded as a single nucleotide polymorphism (rs3207362) in the dbSNP.[8]
Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).
Site
An editing site was found in the pre-mRNA of this protein. The substitution occurs within amino acid position 320 in humans and also in mice.A possible double stranded RNA region has not been detected for this pre-mRNA.[8] No double stranded region required by ADARs has predicted.Immunoprecipitation experiments and RNA interference have shown that ADAR 2 is likely to be the main editing enzyme for this site with ADAR 1 having a minor role.[9][10]
Regulation
Editing seems to be differentially regulated in different tissues. The highest level of editing occurs in the cerebellum with lower frequency of editing detected in human lung, prostrate and uterus tissues. Editing frequency varies from 30-85% depending on tissue.[8][9]{[10] There is some evidence for a decrease in CYFIP2 editing with increased age.[11]
Conservation
Editing of the pre-mRNA of this gene has been detected in mouse and chicken.[8]
Effects of RNA editing
Structural
Editing results in a codon change resulting in a glutamic acid being translated instead of a lysine.[8]
Functional
Currently unknown but editing may have role in regulation of apoptotic functions of this protein.It is thought that since the protein is p53 inducible that the protein may be pro-apopototic. Also ADAR1 knock out mice show increase in apoptosis which indicates editing may be involved in regulation of the cellular process.[6][8]
↑Schenck, A., Bardoni, B., Moro, A., Bagni, C., Mandel, J.-L. (2001) Proceedings of the National Academy of Sciences of the United States of America, 98, 8844-8849.
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