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Identification of regulatory cis ‐acting elements for alternative splicing of presenilin 2 exon 5 under hypoxic stress conditions
Author(s) -
Higashide Satoshi,
Morikawa Keisuke,
Okumura Masayo,
Kondo Shinichi,
Ogata Maiko,
Murakami Tomohiko,
Yamashita Akinori,
Kanemoto Soshi,
Manabe Takayuki,
Imaizumi Kazunori
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02798.x
Subject(s) - exon , rna splicing , alternative splicing , biology , exon trapping , gene , presenilin , rna , genetics , microbiology and biotechnology , alzheimer's disease , medicine , disease
An alternatively spliced form of the presenilin 2 (PS2) gene lacking exon 5 (PS2V) was found in human brains with sporadic Alzheimer's disease. PS2V was induced by hypoxic stress in human neuroblastoma SK‐N‐SH cells, indicating that hypoxic stress affects the splicing machineries for PS2 exon 5. Here, we identified the critical cis ‐acting element (sec 2) on the PS2 pre‐mRNA responsible for the aberrant splicing of PS2 exon 5 under hypoxic stress conditions. The element was composed of 23 nucleotides in exon 5 and RNA structural analyses showed a stem‐loop structure in this sequence. Treatment with an antisense oligonucleotide directed toward the cis ‐acting element caused an increase in exon 5 inclusion. These results indicate that the sec 2 identified in this study is a novel regulatory element for exon 5 splicing under stress conditions and that trans ‐acting factors could specifically bind to the element to skip exon 5 of PS2.