Analysis of the 5' sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease

被引:124
作者
Rogaev, EI
Sherrington, R
Wu, C
Levesque, G
Liang, Y
Rogaeva, EA
Ikeda, M
Holman, K
Lin, C
Lukiw, WJ
deJong, PJ
Fraser, PE
Rommens, JM
StGeorgeHyslop, P
机构
[1] UNIV TORONTO,CTR RES NEURODEGENERAT DIS,DEPT MED NEUROL,TORONTO,ON M5S 1A8,CANADA
[2] UNIV TORONTO,CTR RES NEURODEGENERAT DIS,DEPT MED BIOPHYS,TORONTO,ON M5S 1A8,CANADA
[3] UNIV TORONTO,CTR RES NEURODEGENERAT DIS,DEPT MED & MOL GENET,TORONTO,ON M5S 1A8,CANADA
[4] TORONTO HOSP,DEPT MED,DIV NEUROL,TORONTO,ON M5S 3H2,CANADA
[5] ROSWELL PK CANC INST,BUFFALO,NY 14263
[6] LOUISIANA STATE UNIV,EYE & NEUROSCI CTR,SCH MED,NEW ORLEANS,LA 70112
[7] UNIV TORONTO,HOSP SICK CHILDREN,RES INST,TORONTO,ON M5S 3H2,CANADA
基金
加拿大健康研究院;
关键词
D O I
10.1006/geno.1996.4523
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Mutations in the human presenilin genes (PSEN1 and PSEN2) are associated with early onset familial Alzheimer disease. The presenilin genes encode integral membrane proteins with similar structures, which suggests that they may have closely related, but as yet unknown functions. Analysis of the 5' upstream sequence and the structure of the PSEN1 gene reveals that the 5' sequence contains multiple putative transcription regulatory elements including clusters of STAT elements involved in transcriptional activation in response to signal transduction. The first four exons contain untranslated sequences, with Exons 1 and 2 representing alternate initial transcription sites. The function of these alternate initial exons is unclear. Exon 4 bears the first ATG sequence. The last 12 bp of Exon 4 is used as an alternative splice donor site. Exon 9 is alternately spliced in leukocytes, but not in most other tissues. Splicing of Exon 9 is predicted to cause significant structural changes to the protein The majority of transcripts expressed in most tissues are polyadenylated 1127 bp from the TAG stop codon in Exon 13. A small proportion of transcripts contain the same 5'UTR and ORF but are polyadenylated 4435 bp from the stop codon. The longer polyadenylated transcripts contain three additional palindromes and at least one additional stem-loop structure with stabilities greater than -16 kcal/mol. (C) 1997 Academic Press.
引用
收藏
页码:415 / 424
页数:10
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