Molecular Misreading: A New Type of Transcript Mutation in Gerontology
Identifieur interne : 001C03 ( Main/Exploration ); précédent : 001C02; suivant : 001C04Molecular Misreading: A New Type of Transcript Mutation in Gerontology
Auteurs : Fred W. Van Leeuwen [Pays-Bas] ; David F. Fischer [Pays-Bas] ; Rob Benne [Pays-Bas] ; Elly M. Hol [Pays-Bas]Source :
- Annals of the New York Academy of SciencesMOLECULAR AND CELLULAR GERONTOLOGY [ 0077-8923 ] ; 2000-06.
Abstract
Abstract: Molecular misreading is a novel process that causes mutations in neuronal transcripts.1 It is defined as the inaccurate conversion of genomic information from DNA into nonsense transcripts and the subsequent translation into mutant proteins.2 As a result of dinucleotide deletions (ΔGA, ΔGU, ΔCU) in and around GAGAG motifs in mRNA the reading frame shifts to the +1 rame, and subsequently the so‐called +1 proteins are synthetized. +1 Proteins have a wild‐type NH2 terminus and from the site of the dinucleotide deletion onwards an aberrant, nonfunctional COOH terminus. Molecular misreading was found in the rat vasopressin gene associated with diabetes insipidus 3 and in the human genes linked to Alzheimer's disease (AD), that is, β‐amyloid precursor protein (βAPP) and ubiquitin‐B (UBB).1,2 Moreover, βAPP+1 and UBB+1 proteins accumulate in the neuropathological hallmarks of AD. Inasmuch as these +1 proteins were also found in elderly, nondemented control patients, but not in younger ones (<72 years), molecular misreading may act as a factor that becomes manifest in aged people. A hotspot for dinucleotide deletions is GAGAG motifs. Because statistically an average of 2.1 GAGAG motifs per gene can be expected, other genes expressed in other tissues may undergo molecular misreading as well. Indeed, we recently detected +1 proteins in proliferating cells present in tissues such as the liver, epididymis, parotid gland, and neuroblastoma cell lines.4 Therefore, molecular misreading can be regarded as a general biological source of transcript errors that may be involved in cellular derangements in numerous age‐related pathologic conditions apart from Alzheimer's disease.
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DOI: 10.1111/j.1749-6632.2000.tb06654.x
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Hol</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4AEBE7D7F7B7897D7CFEB1C5A43D28E7269EE92B</idno><date when="2000" year="2000">2000</date><idno type="doi">10.1111/j.1749-6632.2000.tb06654.x</idno><idno type="url">https://api.istex.fr/document/4AEBE7D7F7B7897D7CFEB1C5A43D28E7269EE92B/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002265</idno><idno type="wicri:Area/Main/Curation">001F50</idno><idno type="wicri:Area/Main/Exploration">001C03</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Molecular Misreading: A New Type of Transcript Mutation in Gerontology</title><author><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><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam</wicri:regionArea><wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Fischer, David F" sort="Fischer, David F" uniqKey="Fischer D" first="David F." last="Fischer">David F. Fischer</name><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam</wicri:regionArea><wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Benne, Rob" sort="Benne, Rob" uniqKey="Benne R" first="Rob" last="Benne">Rob Benne</name><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Academic Medical Hospital, Department of Biochemistry, Meibergdreef 15, 1105 AZ Amsterdam</wicri:regionArea><wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion></affiliation></author><author><name sortKey="Hol, Elly M" sort="Hol, Elly M" uniqKey="Hol E" first="Elly M." last="Hol">Elly M. Hol</name><affiliation wicri:level="1"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam</wicri:regionArea><wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the New York Academy of SciencesMOLECULAR AND CELLULAR GERONTOLOGY</title><idno type="ISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2000-06">2000-06</date><biblScope unit="volume">908</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="267">267</biblScope><biblScope unit="page" to="281">281</biblScope></imprint><idno type="ISSN">0077-8923</idno></series><idno type="istex">4AEBE7D7F7B7897D7CFEB1C5A43D28E7269EE92B</idno><idno type="DOI">10.1111/j.1749-6632.2000.tb06654.x</idno><idno type="ArticleID">NYAS267</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0077-8923</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Molecular misreading is a novel process that causes mutations in neuronal transcripts.1 It is defined as the inaccurate conversion of genomic information from DNA into nonsense transcripts and the subsequent translation into mutant proteins.2 As a result of dinucleotide deletions (ΔGA, ΔGU, ΔCU) in and around GAGAG motifs in mRNA the reading frame shifts to the +1 rame, and subsequently the so‐called +1 proteins are synthetized. +1 Proteins have a wild‐type NH2 terminus and from the site of the dinucleotide deletion onwards an aberrant, nonfunctional COOH terminus. Molecular misreading was found in the rat vasopressin gene associated with diabetes insipidus 3 and in the human genes linked to Alzheimer's disease (AD), that is, β‐amyloid precursor protein (βAPP) and ubiquitin‐B (UBB).1,2 Moreover, βAPP+1 and UBB+1 proteins accumulate in the neuropathological hallmarks of AD. Inasmuch as these +1 proteins were also found in elderly, nondemented control patients, but not in younger ones (<72 years), molecular misreading may act as a factor that becomes manifest in aged people. A hotspot for dinucleotide deletions is GAGAG motifs. Because statistically an average of 2.1 GAGAG motifs per gene can be expected, other genes expressed in other tissues may undergo molecular misreading as well. Indeed, we recently detected +1 proteins in proliferating cells present in tissues such as the liver, epididymis, parotid gland, and neuroblastoma cell lines.4 Therefore, molecular misreading can be regarded as a general biological source of transcript errors that may be involved in cellular derangements in numerous age‐related pathologic conditions apart from Alzheimer's disease.</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. 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