Alternative promoter usage generates novel ...
Document type :
Article dans une revue scientifique: Article original
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Title :
Alternative promoter usage generates novel shorter mapt mrna transcripts in alzheimer's disease and progressive supranuclear palsy brains
Author(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
Journal title :
Scientific reports
Abbreviated title :
Sci Rep
Volume number :
7
Publication date :
2017-10-03
ISSN :
2045-2322
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Submission date :
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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