The human MAPT locus generates circular RNAs.
Biochim Biophys Acta Mol Basis Dis
; 1864(9 Pt B): 2753-2760, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29729314
ABSTRACT
The microtubule-associated protein Tau, generated by the MAPT gene is involved in dozens of neurodegenerative conditions ("tauopathies"), including Alzheimer's disease (AD) and frontotemporal lobar degeneration/frontotemporal dementia (FTLD/FTD). The pre-mRNA of MAPT is well studied and its aberrant pre-mRNA splicing is associated with frontotemporal dementia. Using a PCR screen of RNA from human brain tissues, we found that the MAPT locus generates circular RNAs through a backsplicing mechanism from exon 12 to either exon 10 or 7. MAPT circular RNAs are localized in the cytosol and contain open reading frames encoding Tau protein fragments. The MAPT exon 10 is alternatively spliced and proteins involved in its regulation, such as CLK2, SRSF7/9G8, PP1 (protein phosphatase 1) and NIPP1 (nuclear inhibitor of PP1) reduce the abundance of the circular MAPT exon 12â¯ââ¯10 backsplice RNA after being transfected into cultured HEK293 cells. In summary, we report the identification of new bona fide human brain RNAs produced from the MAPT locus. These may be a component of normal human brain Tau regulation and, since the circular RNAs could generate high molecular weight proteins with multiple microtubule binding sites, they could contribute to taupathies.
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Base de dados:
MEDLINE
Assunto principal:
RNA
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Precursores de RNA
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Proteínas tau
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Tauopatias
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Demência Frontotemporal
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article