FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10
FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10
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DOI：
10.1016/s0014-5793(98)01696-2
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发表时间：
1999-01-25
期刊：
影响因子：
3.5
通讯作者：
Goedert, M
中科院分区：
文献类型：
--
作者：
Hasegawa, M;Smith, MJ;Goedert, M
错义突变和tau基因的内含子突变导致与17号染色体（FTDP-17）相关的额颞叶痴呆和帕金森综合征。已知的错义突变降低了tau促进微管组装的能力。内含子突变导致可变剪接外显子10的mRNA剪接增加，导致具有四个微管结合重复的tau亚型的过度产生。我们在这里表明，最近确定的FTDP-17错义突变N279 K和S305 N不会降低tau蛋白促进微管组装的能力。相反，它们导致外显子10的剪接增加，如内含子突变。N279 K和S305 N突变定义了tau蛋白中的一类错义突变，其主要作用是在RNA水平。(C)1999年欧洲生物化学学会联合会。
Missense mutations and intronic mutations in the tau gene cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known missense mutations reduce the ability of tau to promote microtubule assembly. Intronic mutations lead to increased mRNA splicing of the alternatively spliced exon 10, resulting in an overproduction of tau isoforms with four microtubule-binding repeats. We show here that the recently identified FTDP-17 missense mutations N279K and S305N do not reduce the ability of tau to promote microtubule assembly. Instead they lead to increased splicing of exon 10, like the intronic mutations. The N279K and S305N mutations define a class of missense mutations in tau whose primary effects are at the RNA level. (C) 1999 Federation of European Biochemical Societies.