The RNA-binding fragile-X mental retardation protein and its role beyond the brain.

RNA 结合脆性 X 智力低下蛋白及其在大脑之外的作用。

• 发表时间: Aug 2020
• 来源期刊: Biophys Rev
• DOI: 10.1007/s12551-020-00730-4
• PMID: 32654068
• 文章类型: Journal Article
• 作者列表: Malecki C,Hambly BD,Jeremy RW,Robertson EN

关键词: Fragile-X; RNA-binding protein; Repeat expansion

Abstract

It is well-established that variations of a CGG repeat expansion in the gene FMR1, which encodes the fragile-X mental retardation protein (FMRP), cause the neurocognitive disorder, fragile-X syndrome (FXS). However, multiple observations suggest a general and complex regulatory role of FMRP in processes outside the brain: (1) FMRP is ubiquitously expressed in the body, suggesting it functions in multiple organ systems; (2) patients with FXS can exhibit a physical phenotype that is consistent with an underlying abnormality in connective tissue; (3) different CGG repeat expansion lengths in FMR1 result in different clinical outcomes due to different pathogenic mechanisms; (4) the function of FMRP as an RNA-binding protein suggests it has a general regulatory role. This review details the complex nature of FMRP and the different CGG repeat expansion lengths and the evidence supporting the essential role of the protein in a variety of biological and pathological processes.