Feng Y, Absher D, Eberhart D E, Brown V, Malter H E, Warren S T
Howard Hughes Medical Institute, Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Mol Cell. 1997 Dec;1(1):109-18. doi: 10.1016/s1097-2765(00)80012-x.
Fragile X mental retardation is caused by the lack of FMRP, a selective RNA-binding protein associated with ribosomes. A missense mutation, I304N, has been found to result in an unusually severe phenotype. We show here that normal FMRP associates with elongating polyribosomes via large mRNP particles. Despite normal expression and cytoplasmic mRNA association, the I304N FMRP is incorporated into abnormal mRNP particles that are not associated with polyribosomes. These data indicate that association of FMRP with polyribosomes must be functionally important and imply that the mechanism of the severe phenotype in the I304N patient lies in the sequestration of bound mRNAs in nontranslatable mRNP particles. In the absence of FMRP, these same mRNAs may be partially translated via alternative mRNPs, although perhaps abnormally localized or regulated, resulting in typical fragile X syndrome.
脆性X智力障碍是由FMRP缺乏引起的，FMRP是一种与核糖体相关的选择性RNA结合蛋白。已发现一种错义突变I304N会导致异常严重的表型。我们在此表明，正常的FMRP通过大型mRNP颗粒与延伸中的多核糖体结合。尽管I304N FMRP的表达正常且与细胞质mRNA结合，但它被整合到与多核糖体无关的异常mRNP颗粒中。这些数据表明，FMRP与多核糖体的结合在功能上一定很重要，并且暗示I304N患者严重表型的机制在于将结合的mRNA隔离在不可翻译的mRNP颗粒中。在没有FMRP的情况下，这些相同的mRNA可能通过替代的mRNP进行部分翻译，尽管可能定位异常或调控异常，从而导致典型的脆性X综合征。
