The RAY1/ST7 tumor-suppressor locus on chromosome 7q31 represents a complex multi-transcript system.
We recently identified a novel gene, RAY1 (FAM4A1), which spans a translocation breakpoint at 7q31 in a patient with autism. This gene has more recently been reported to be a suppressor of tumorigenicity, ST7, although controversy surrounds this observation because subsequent reports have failed to corroborate these findings. Our further analysis of this locus reveals that it is composed of a multigene system that includes two noncoding sense strand genes (ST7OT3 and ST7OT4) that overlap with many alternative forms of the coding RAY1/ST7 transcript, and two noncoding genes on the antisense strand (ST7OT1 and ST7OT2). RAY1/ST7 was determined to have at least three different 5' exons with alternative start codons, one of which seems to be used almost exclusively in the brain. We have also identified a third alternative 3' end of RAY1/ST7 that uses exons from ST7OT3. ST7OT3 spans from intron 10 to exon 14 of RAY1/ST7 and includes several exons. ST7OT4 has at least seven exons and is transcribed on the sense strand between RAY1/ST7 exon 1 and a tropomyosin-like sequence, TPM3L2. ST7OT1 overlaps with the RAY1/ST7 exon 1 and promoter. ST7OT2 spans from RAY1/ST7 intron 9 to intron 1, and has multiple isoforms. We screened the exons of RAY1/ST7 and ST7OT1-3 for sequence variants in 90 unrelated autism probands and identified several rare variants, including a Ile361Val substitution. Although these variants were not observed in a control population, it is unclear whether they contribute to the autistic phenotype. We postulate that the apparent noncoding genes at the RAY1/ST7 locus may be regulatory RNAs. The RAY1/ST7 may generate at least 18 possible isoforms, with many more arising if other sense-strand exons from ST7OT3 and ST7 OT4 are used in a selective and possibly tissue-specific manner.
Vincent
John B
JB
Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, M5G 1X8, Canada. jvincent@genet.sickkids.on.ca
Petek
Erwin
E
Thevarkunnel
Sandy
S
Kolozsvari
Debbie
D
Cheung
Joseph
J
Patel
Megha
M
Scherer
Stephen W
SW
D017398:Alternative Splicing; D002897:Chromosomes, Human, Pair 7; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins
D020033:Protein Isoforms; D011506:Proteins; C412123:ST7 protein, human; D025521:Tumor Suppressor Proteins