Alternative promoter usage generates novel ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Alternative promoter usage generates novel shorter mapt mrna transcripts in alzheimer's disease and progressive supranuclear palsy brains
Auteur(s) :
Huin, Vincent [Auteur]
Buee, Luc [Auteur]
Behal, Helene [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Labreuche, Julien [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Sablonniere, Bernard [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Lille Neurosciences & Cognition (LilNCog) - U 1172
DHAENENS, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Buee, Luc [Auteur]
Behal, Helene [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Labreuche, Julien [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Sablonniere, Bernard [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Lille Neurosciences & Cognition (LilNCog) - U 1172
DHAENENS, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Titre de la revue :
Scientific reports
Nom court de la revue :
Sci Rep
Numéro :
7
Date de publication :
2017-10-03
ISSN :
2045-2322
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and ...
Lire la suite >Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.Lire moins >
Lire la suite >Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Date de dépôt :
2019-12-09T16:49:14Z
2020-03-23T09:44:06Z
2020-03-24T13:57:13Z
2020-03-24T14:20:08Z
2020-03-23T09:44:06Z
2020-03-24T13:57:13Z
2020-03-24T14:20:08Z
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