Species-specific and isoform-specific RNA binding of human and mouse fragile X mental retardation proteins

Biochem Biophys Res Commun. 2002 Apr 12;292(4):1063-9. doi: 10.1006/bbrc.2002.6768.


The loss of the fragile X RNA binding protein, FMRP, causes macroorchidism and mental retardation in man. The discovery of a mouse ortholog led to the development of several FMRP knockout mouse strains that recapitulate some features of the disease. As mouse and human FMRPs differ in several amino acids in their RNA binding domains, we compared the RNA binding profiles of these two orthologs. Five variant FMRPs, whose differences arose from alternative splicing and mutation within the conserved RNA binding domains, were examined. Homoribopolymer binding studies showed that human FMRPs (hFMRP) bound a broader range of single-stranded mimetics than mouse FMRPs (mFMRP) and these interactions were both complex and cooperative. hFMRP and mFMRP also displayed significant preferences toward binding their own mRNA; specifically we found that the mFMRP isoforms bind mFMR1 mRNA much more tightly than their human counterparts. Finally, these data demonstrate that each FMRP variant binds RNAs uniquely, resulting in a set of proteins with differing affinities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / genetics
  • Cell-Free System
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome* / genetics
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Poly A / chemistry
  • Poly A / metabolism
  • Poly C / chemistry
  • Poly C / metabolism
  • Poly G / chemistry
  • Poly G / metabolism
  • Poly U / chemistry
  • Poly U / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sodium Chloride / pharmacology
  • Species Specificity


  • FMR1 protein, human
  • Fmr1 protein, mouse
  • Nerve Tissue Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein
  • Poly A
  • Poly G
  • Poly U
  • Poly C
  • Sodium Chloride
  • RNA