Tau Isoforms: Gaining Insight into MAPT Alternative Splicing
Abstract
:1. Introduction
2. MAPT Gene Organization and Alternatively Spliced Transcripts
3. Tau Isoforms
3.1. Functional Domains Characterizing Tau Protein
3.2. Central Nervous System (CNS) Isoforms
3.3. Big-Tau
3.4. Isoforms including Exon 6
3.5. W-Tau
4. Tau and Cancer
5. Human MAPT Mutations Causing Aberrant Tau Splicing in Tauopathies
6. Alternative Splicing Regulation of Tau Exons
Tau Splicing and Ribonucleoproteins
RBP | Tau Exon Regulation | Ref. |
---|---|---|
LUC7L3 | Exon 10 | [133] |
THRAP3 | Exon 10 | [133] |
SRSF1, SRSF2, SRSF3, SRSF4, SRSF6, SRSF7, SRSF9, SRSF11 | Exon 10 | [24,48,130,154] |
EMG1 | Exon 10 | [133] |
PRPF19 | Exon 10 | [133] |
ARL6IP4 | Exon 10 | [133] |
DHX15, 21 | Exon 10 | [133] |
SLM1, SLM2 | Exon 6 | [151] |
hnRNPU, D, A3, HI, C, R, A2B1, A1, G, E2 (PCBP2) | Exon 6, exon 10 | [133,151,155] |
CLF4, CLF5, CLF6 | Exon 6, exon 10 | [39] |
SC35 | Exon6, exon 10 | [151,156] |
YT521B | Exon 6 | [151] |
ASF | Exon 6 | [151] |
Htra2β1 | Exon 6, exon 10 | [48,129,151] |
9G8 | Exon 6 | [151] |
PTBP1 | Exon 6, exon 10 | [142,151] |
PTBP2 | Exon 6 | [151] |
SRSF3, SRSF5, SRSF6, SRSF4, SRSF9, | Exon6 | [151] |
Swap | Exon 6 | [151] |
Nova 1 | Exon 6 | [151] |
U2AF | Exon 6 | [151] |
SFPQ | Exon 10 | [141] |
RBM4 | Exon 10 | [140] |
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Minigene Name | Exon(s) | Properties | Application | Ref. |
---|---|---|---|---|
hTau | 1, 2, 4 | Exon 2 flanked by different length of its native introns, surrounded by E1 and E4 | Identification of cis and trans acting elements altering splicing of E2 | [132] |
SV1/2L/4 | 2 | Exon 2 flanked by its native exons | In situ mutagenesis to identify cis acting elements in the exon and downstream intron | [36] |
SP/2L | 2 | Exon 2 flanked by heterologous exons | In situ mutagenesis to identify cis acting elements in the exon and downstream intron | [36] |
SVΔ2/3 | 3 | E3, 1.1 kbps of I2 and 1.4 kpbs of I3 | E3 default splicing pattern analysis, identification of cis-acting elements | [37] |
pSVIRB SV6 | 6 | E6, 600 bps I5, 200 bps I6 | Exon-trapping assay | [40] |
TauEx9-11d5 | 9-10-11 | E10 flanked by 269 and 246 bp of its native intron and exons 9–11. | Identification of cis-acting elements altering splicing of E10 | [129] |
SI9/SI10 LI9/SI10 SI9/LI10 LI9/LI10 | 9-10-11 | E10 can be flanked by a long (L) or short (S) portion of the upstream and downstream intron | Identification of a required minimal distance for E10 splicing | [130] |
Tau minigene | 9-10-11 | Identification of HnRNPC as a novel trans-acting factor on E10 | [133] | |
RHCGlo Tau wt RHCGlo Tau Δ280K RHCGlo Tau N279K | 10 | Contains WT E10 or E10 with Δ280K, and N279K mutations | Identification of cis and trans-acting elements affecting E10 splicing | [128] |
Luc M14 | 10 | Luciferase reporter, modified from TauEx9-11 d5 minigene | Identification of compound that reduced exon 10 inclusion; identify cis/trans elements | [130,131,134,135] |
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Corsi, A.; Bombieri, C.; Valenti, M.T.; Romanelli, M.G. Tau Isoforms: Gaining Insight into MAPT Alternative Splicing. Int. J. Mol. Sci. 2022, 23, 15383. https://doi.org/10.3390/ijms232315383
Corsi A, Bombieri C, Valenti MT, Romanelli MG. Tau Isoforms: Gaining Insight into MAPT Alternative Splicing. International Journal of Molecular Sciences. 2022; 23(23):15383. https://doi.org/10.3390/ijms232315383
Chicago/Turabian StyleCorsi, Andrea, Cristina Bombieri, Maria Teresa Valenti, and Maria Grazia Romanelli. 2022. "Tau Isoforms: Gaining Insight into MAPT Alternative Splicing" International Journal of Molecular Sciences 23, no. 23: 15383. https://doi.org/10.3390/ijms232315383