title: An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals.
abstract: Expansion of the polymorphic CGG repeats within the 5'-UTR of the FMR1 gene is associated with variable transcriptional regulation of FMR1. Here we report a novel gene, ASFMR1, overlapping the CGG repeat region of FMR1 and transcribed in the antisense orientation. The ASFMR1 transcript is spliced, polyadenylated and exported to the cytoplasm. Similar to FMR1, ASFMR1 is upregulated in individuals with premutation alleles and is not expressed from full mutation alleles. Moreover, it exhibits premutation-specific alternative splicing. Taken together, these observations suggest that in addition to FMR1, ASFMR1 may contribute to the variable phenotypes associated with the CGG repeat expansion.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Paula D
authors.initials: PD
authors.lastname: Ladd
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Smith
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Rabaia
authors.forename: James M
authors.initials: JM
authors.lastname: Moore
authors.forename: Sara A
authors.initials: SA
authors.lastname: Georges
authors.forename: R Scott
authors.initials: RS
authors.lastname: Hansen
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott
authors.forename: Galina N
authors.initials: GN
authors.lastname: Filippova
mesh_terms: D017398:Alternative Splicing / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010455:Peptides / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014018:Tissue Distribution; D018911:Trinucleotide Repeats; D015854:Up-Regulation
chemical_list: D000076246:CCCTC-Binding Factor; D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D010455:Peptides; D016372:RNA, Antisense; D012097:Repressor Proteins; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C497683:FMR1 protein, human; C011083:polyproline