TY - JOUR
T1 - Ataxia-telangiectasia
T2 - structural diversity of untranslated sequences suggests complex post-transcriptional regulation of ATM gene expression
AU - Savitsky, Kinneret
AU - Platzer, Matthias
AU - Uziel, Tamar
AU - Gilad, Shlomit
AU - Sartiel, Adam
AU - Rosenthal, Andre
AU - Elroy-Stein, Orna
AU - Shiloh, Yosef
AU - Rotman, Galit
N1 - Funding Information:
This study was supported by research grants from the A-T Children’s Project, the A-T Medical Research Foundation, the United States–Israel Binational Science Foundation and the National Institute of Neurological Disorders and Stroke (NS31763). This work was carried out in partial fulfillment of the requirements for the Ph.D. degree to K.S.
PY - 1997/5/1
Y1 - 1997/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030871226&partnerID=8YFLogxK
U2 - 10.1093/nar/25.9.1678
DO - 10.1093/nar/25.9.1678
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AN - SCOPUS:0030871226
SN - 0305-1048
VL - 25
SP - 1678
EP - 1684
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 9
ER -
