2014
DOI: 10.1007/s12264-013-1411-2
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Regulation of alternative splicing of tau exon 10

Abstract: The neuronal microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in the brains of individuals with Alzheimer's disease and related neurodegenerative disorders. The adult human brain expresses six isoforms of tau generated by alternative splicing of exons 2, 3, and 10 of its pre-mRNA. Exon 10 encodes the second microtubule-binding repeat of tau. Its alternative splicing produces tau isoforms with either three or four microtubule-binding repeats, terme… Show more

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Cited by 87 publications
(88 citation statements)
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“…The high number of samples analyzed in that study allowed them to conclude that the top increment takes place in grade 2 cases regarding the mRNA and in grade 3 cases regarding the protein, resulting in higher 0N4R and lower 1N3R isoforms (St-Amour et al, 2018). All these findings regarding altered isoform ratio in HD are very relevant in view of the fact that alteration in the ratio of 4R-Tau and 3R-Tau isoforms is sufficient to cause neurodegeneration (Hutton et al, 1998;Qian and Liu, 2014), as this might contribute per se to HD neurodegeneration independently of other deleterious effects of mHtt, thus becoming a therapeutic target for HD.…”
Section: Aberrant Splicing Of Tau In Hdmentioning
confidence: 82%
“…The high number of samples analyzed in that study allowed them to conclude that the top increment takes place in grade 2 cases regarding the mRNA and in grade 3 cases regarding the protein, resulting in higher 0N4R and lower 1N3R isoforms (St-Amour et al, 2018). All these findings regarding altered isoform ratio in HD are very relevant in view of the fact that alteration in the ratio of 4R-Tau and 3R-Tau isoforms is sufficient to cause neurodegeneration (Hutton et al, 1998;Qian and Liu, 2014), as this might contribute per se to HD neurodegeneration independently of other deleterious effects of mHtt, thus becoming a therapeutic target for HD.…”
Section: Aberrant Splicing Of Tau In Hdmentioning
confidence: 82%
“…has been studied in relation to the balance between 3R and 4R tau in AD and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) (37). Many intron mutations in the MAPT tau gene have been found in FTDP-17, and they are reported to increase the expression ratio of 4R tau (37,38). It has been shown that the splicing in or out activity of exon 10 is regulated by the phosphorylation of serine/arginine-rich (SR) proteins in the spliceosome (39).…”
Section: Developmental Regulation Of Tau Isoforms and Phosphorylationmentioning
confidence: 99%
“…It has been shown that the splicing in or out activity of exon 10 is regulated by the phosphorylation of serine/arginine-rich (SR) proteins in the spliceosome (39). Although there are protein kinases that are relatively specific for SR splicing proteins, such as SR protein kinase or Cdc-like kinase (CLK/Sly) (38,39), several tau protein kinases, including GSK3␤, DYRK1, and PKA, are also reported to regulate the splicing of tau pre-mRNA by phosphorylating the particular splicing proteins (40 -44). Although their involvement in the developmental regulation of tau isoforms has not been investigated, some of these protein kinases could regulate both the splicing of tau pre-mRNA and the phosphorylation of tau protein.…”
Section: Developmental Regulation Of Tau Isoforms and Phosphorylationmentioning
confidence: 99%
“…During AS of precursor mRNA (premRNA), different combinations of 5' and 3' splice site pairs are selected, resulting in the generation of divers mRNA and protein variants. Pre-mRNA splicing takes place within the spliceosome, a large molecular complex composed of five small nuclear ribonucleoproteins (snRNPs) U1, U2, U4, U5, U6, and approximately 50-100 non-snRNP splicing factors [18]. The spliceosome recognizes specific sequences in pre-mRNA to define intron-exon boundaries and to facilitate splicing.…”
Section: Alternative Splicingmentioning
confidence: 99%
“…Furthermore, splicing is regulated by specific nucleotide sequences found within the mRNA (cis-elements). These elements include exonic splicing enhancers, exonic splicing silencers, and intronic splicing silencers [18]. In addition to cis-elements, trans-acting factors are a group of proteins that bind to cis-elements and are composed of serine and arginine rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs).…”
Section: Alternative Splicingmentioning
confidence: 99%