Fragile X mental retardation protein (FMRP) binds specifically to the brain cytoplasmic RNAs BC1/BC200 via a novel RNA-binding motif

J Biol Chem. 2005 Sep 30;280(39):33403-10. doi: 10.1074/jbc.M504286200. Epub 2005 Jul 8.

Abstract

Fragile X mental retardation protein (FMRP), the protein responsible for the fragile X syndrome, is an RNA-binding protein involved in localization and translation of neuronal mRNAs. One of the RNAs known to interact with FMRP is the dendritic non-translatable brain cytoplasmic RNA 1 BC1 RNA that works as an adaptor molecule linking FMRP and some of its regulated mRNAs. Here, we showed that the N terminus of FMRP binds strongly and specifically to BC1 and to its potential human analog BC200. This region does not contain a motif known to specifically recognize RNA and thus constitutes a new RNA-binding motif. We further demonstrated that FMRP recognition involves the 5' stem loop of BC1 and that this is the region that exhibits complementarity to FMRP target mRNAs, raising the possibility that FMRP plays a direct role in BC1/mRNA annealing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Brain / metabolism*
  • Cross-Linking Reagents / pharmacology
  • Cytoplasm / metabolism*
  • Dendrites / metabolism
  • Electrophoretic Mobility Shift Assay
  • Fragile X Syndrome / metabolism
  • Gene Deletion
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Neurons / metabolism
  • Protein Structure, Tertiary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Cytoplasmic / chemistry
  • RNA, Small Cytoplasmic / genetics
  • RNA, Small Cytoplasmic / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ultraviolet Rays

Substances

  • BC1 RNA
  • Cross-Linking Reagents
  • RNA, Messenger
  • RNA, Small Cytoplasmic
  • RNA-Binding Proteins