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Analysis of the 5′ Sequence, Genomic Structure, and Alternative Splicing of thepresenilin-1Gene (PSEN1) Associated with Early Onset Alzheimer Disease
Ist Teil von
Genomics (San Diego, Calif.), 1997-03, Vol.40 (3), p.415-424
Ort / Verlag
Elsevier Inc
Erscheinungsjahr
1997
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
Mutations in the human presenilin genes (PSEN1andPSEN2) 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 thePSEN1gene 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.