Molecular misreading: a new type of transcript mutation expressed during aging
Identifieur interne : 001C01 ( Main/Exploration ); précédent : 001C00; suivant : 001C02Molecular misreading: a new type of transcript mutation expressed during aging
Auteurs : Fred W. Van Leeuwen [Pays-Bas] ; David F. Fischer [Pays-Bas] ; Darlene Kamel [Pays-Bas] ; Jacqueline A. Sluijs [Pays-Bas] ; Marc A. F. Sonnemans [Pays-Bas] ; Rob Benne [Pays-Bas] ; Dick F. Swaab [Pays-Bas] ; Ahmad Salehi [Pays-Bas] ; Elly M. Hol [Pays-Bas]Source :
- Neurobiology of Aging [ 0197-4580 ] ; 2000.
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Abstract
Dinucleotide deletions (e.g. ΔGA, ΔGU) are created by molecular misreading in or adjacent to GAGAG motifs of neuronal mRNAs. As a result, the reading frame shifts to the +1 frame, and so-called “+1 proteins” are subsequently synthesized. +1 Proteins have a wild-type N-terminus, but an aberrant C-terminus downstream from the site of the dinucleotide deletion. Molecular misreading was discovered in the rat vasopressin gene associated with diabetes insipidus and subsequently in human genes linked to Alzheimer’s disease (AD), e.g. β amyloid precursor protein (βAPP) and ubiquitin-B (UBB). Furthermore, βAPP+1 and UBB+1 proteins accumulate in the neuropathological hallmarks (i.e. in the tangles, neuritic plaques, and neuropil threads) of AD. As these +1 proteins were also found in elderly nondemented controls, but not in younger ones (<51 years), molecular misreading in nondividing cells might act as a factor that only becomes manifest at an advanced age. Frameshift mutations (UBB+1) and pretangle staining (Alz-50 and MC1) seem to occur independently of each other during early stages of AD. We recently detected +1 proteins, not only in proliferating cells present in non-neuronal tissues such as the liver and epididymis, but also in neuroblastoma cell lines. These observations suggest that molecular misreading is a general source of transcript errors that are involved in cellular derangements in various age-related pathologies.
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DOI: 10.1016/S0197-4580(00)00151-2
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We recently detected +1 proteins, not only in proliferating cells present in non-neuronal tissues such as the liver and epididymis, but also in neuroblastoma cell lines. These observations suggest that molecular misreading is a general source of transcript errors that are involved in cellular derangements in various age-related pathologies.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Van Leeuwen, Fred W" sort="Van Leeuwen, Fred W" uniqKey="Van Leeuwen F" first="Fred W." last="Van Leeuwen">Fred W. Van Leeuwen</name></noRegion><name sortKey="Benne, Rob" sort="Benne, Rob" uniqKey="Benne R" first="Rob" last="Benne">Rob Benne</name><name sortKey="Fischer, David F" sort="Fischer, David F" uniqKey="Fischer D" first="David F." last="Fischer">David F. Fischer</name><name sortKey="Hol, Elly M" sort="Hol, Elly M" uniqKey="Hol E" first="Elly M." last="Hol">Elly M. Hol</name><name sortKey="Kamel, Darlene" sort="Kamel, Darlene" uniqKey="Kamel D" first="Darlene" last="Kamel">Darlene Kamel</name><name sortKey="Salehi, Ahmad" sort="Salehi, Ahmad" uniqKey="Salehi A" first="Ahmad" last="Salehi">Ahmad Salehi</name><name sortKey="Sluijs, Jacqueline A" sort="Sluijs, Jacqueline A" uniqKey="Sluijs J" first="Jacqueline A." last="Sluijs">Jacqueline A. Sluijs</name><name sortKey="Sonnemans, Marc A F" sort="Sonnemans, Marc A F" uniqKey="Sonnemans M" first="Marc A. F." last="Sonnemans">Marc A. F. Sonnemans</name><name sortKey="Swaab, Dick F" sort="Swaab, Dick F" uniqKey="Swaab D" first="Dick F." last="Swaab">Dick F. Swaab</name><name sortKey="Van Leeuwen, Fred W" sort="Van Leeuwen, Fred W" uniqKey="Van Leeuwen F" first="Fred W." last="Van Leeuwen">Fred W. Van Leeuwen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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