FRAXE is a form of mild to moderate mental retardation due to the silencing of the FMR2 gene. The cellular function of FMR2 protein is presently unknown. By analogy with its homologue AF4, FMR2 was supposed to have a role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that FMR2 co-localizes with the splicing factor SC35 in nuclear speckles, the nuclear regions where splicing factors are concentrated, assembled and modified. Similarly to what was reported for splicing factors, blocking splicing or transcription leads to the accumulation of FMR2 in enlarged, rounded speckles. FMR2 is also localized in the nucleolus when splicing is blocked. We show here that FMR2 is able to specifically bind the G-quartet-forming RNA structure with high affinity. Remarkably, in vivo, in the presence of FMR2, the ESE action of the G-quartet situated in mRNA of an alternatively spliced exon of a minigene or of the putative target FMR1 appears reduced. Interestingly, FMR1 is silenced in the fragile X syndrome, another form of mental retardation. All together, our findings strongly suggest that FMR2 is an RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure.
Interacting selectively and non-covalently with G-quadruplex RNA structures, in which groups of four guanines adopt a flat, cyclic hydrogen-bonding arrangement known as a guanine tetrad.
The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
Five folate-sensitive fragile sites have been identified at the molecular level to date. Each is characterized by an expanded and methylated trinucleotide repeat CGG (CCG). Of the three X chromosome sites, FRAXA, FRAXE and FRAXF, the former two are associated with mental retardation in their expanded forms. FRAXA expansion results in fragile X syndrome due to down regulation of expression of the FMR1 gene, which carries the hypermutable CGG repeat in the 5' untranslated portion of its first exon. Mild mental retardation without consistent physical findings has been found associated with expanded CCG repeats at FRAXE. We have identified a large gene (FMR2) transcribed distally from the CpG island at FRAXE, and down-regulated by repeat expansion and methylation. The gene is novel, expressed in adult brain and placenta, and shows similarity with another human protein, MLLT2, expressed from a gene at chromosome 4q21 involved in translocations found in acute lymphoblastic leukaemia (ALL) cells. Identification of this gene will facilitate further studies to determine the role of its product in FRAXE associated mental deficiency.
Any process that modulates the frequency, rate or extent of RNA splicing, the process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
FRAXE is a form of mild to moderate mental retardation due to the silencing of the FMR2 gene. The cellular function of FMR2 protein is presently unknown. By analogy with its homologue AF4, FMR2 was supposed to have a role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that FMR2 co-localizes with the splicing factor SC35 in nuclear speckles, the nuclear regions where splicing factors are concentrated, assembled and modified. Similarly to what was reported for splicing factors, blocking splicing or transcription leads to the accumulation of FMR2 in enlarged, rounded speckles. FMR2 is also localized in the nucleolus when splicing is blocked. We show here that FMR2 is able to specifically bind the G-quartet-forming RNA structure with high affinity. Remarkably, in vivo, in the presence of FMR2, the ESE action of the G-quartet situated in mRNA of an alternatively spliced exon of a minigene or of the putative target FMR1 appears reduced. Interestingly, FMR1 is silenced in the fragile X syndrome, another form of mental retardation. All together, our findings strongly suggest that FMR2 is an RNA-binding protein, which might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure.
The process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA.
Protein involved in the processing of the primary mRNA transcript to yield a functional mRNA. This includes 5' capping, 3' cleavage and polyadenylation, as well as mRNA splicing and RNA editing.
Protein involved in the process by which nonsense sequences or intervening sequences (introns) are removed from pre-mRNA to generate a functional mRNA (messenger RNA) that contains only exons.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
My favorites 
My labels 
Login
