title: Ataxia-telangiectasia: structural diversity of untranslated sequences suggests complex post-transcriptional regulation of ATM gene expression.
abstract: Mutations in the ATM gene are responsible for the multisystem disorder ataxia-telangiectasia, characterized by neurodegeneration, immune deficiency and cancer predisposition. While no alternative splicing was identified within the coding region, the first four exons of the ATM gene, which fall within the 5'untranslated region (UTR), undergo extensive alternative splicing. We identified 12 different 5'UTRs that show considerable diversity in length and sequence contents. These mRNA leaders, which range from 150 to 884 nucleotides (nt), are expected to form variable secondary structures and contain different numbers of AUG codons. The longest 5'UTR contains a total of 18 AUGs upstream of the translation start site. The 3'UTR of 3590 nt is contained within a single 3'exon. Alternative polyadenylation results in 3'UTRs of varying lengths. These structural features suggest that ATM expression might be subject to complex post-transcriptional regulation, enabling rapid modulation of ATM protein level in response to environmental stimuli or alterations in cellular physiological states.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Savitsky
authors.forename: M
authors.initials: M
authors.lastname: Platzer
authors.forename: T
authors.initials: T
authors.lastname: Uziel
authors.forename: S
authors.initials: S
authors.lastname: Gilad
authors.forename: A
authors.initials: A
authors.lastname: Sartiel
authors.forename: A
authors.initials: A
authors.lastname: Rosenthal
authors.forename: O
authors.initials: O
authors.lastname: Elroy-Stein
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
authors.forename: G
authors.initials: G
authors.lastname: Rotman
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D004247:DNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases