FMRP ribonucleoprotein complexes and RNA homeostasis

Adv Genet. 2020;105:95-136. doi: 10.1016/bs.adgen.2020.01.001. Epub 2020 Feb 6.

Abstract

The Fragile Mental Retardation 1 gene (FMR1), at Xq27.3, encodes the fragile mental retardation protein (FMRP), and displays in its 5'-untranslated region a series of polymorphic CGG triplet repeats that may undergo dynamic mutation. Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability among men, and is most frequently due to FMR1 full mutation and consequent transcription repression. FMR1 premutations may associate with at least two other clinical conditions, named fragile X-associated primary ovarian insufficiency (FXPOI) and tremor and ataxia syndrome (FXTAS). While FXPOI and FXTAS appear to be mediated by FMR1 mRNA accumulation, relative reduction of FMRP, and triplet repeat translation, FXS is due to the lack of the RNA-binding protein FMRP. Besides its function as mRNA translation repressor in neuronal and stem/progenitor cells, RNA editing roles have been assigned to FMRP. In this review, we provide a brief description of FMR1 transcribed microsatellite and associated clinical disorders, and discuss FMRP molecular roles in ribonucleoprotein complex assembly and trafficking, as well as aspects of RNA homeostasis affected in FXS cells.

Keywords: Autism Spectrum disorder; FMR1; FMRP; FXPOI; FXTAS; RNA; fragile X syndrome; ribonucleoprotein complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia / genetics*
  • Ataxia / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / metabolism
  • Homeostasis / genetics*
  • Humans
  • Male
  • Mutation
  • Primary Ovarian Insufficiency / genetics*
  • Primary Ovarian Insufficiency / metabolism
  • RNA / genetics
  • RNA / metabolism*
  • RNA Editing
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism
  • Tremor / genetics*
  • Tremor / metabolism

Substances

  • FMR1 protein, human
  • Ribonucleoproteins
  • Fragile X Mental Retardation Protein
  • RNA

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome