Interplay between FMRP and lncRNA TUG1 regulates axonal development through mediating SnoN-Ccd1 pathway

Hum Mol Genet. 2018 Feb 1;27(3):475-485. doi: 10.1093/hmg/ddx417.

Abstract

LncRNAs have recently emerged to influence the pathogenesis of fragile X syndrome (FXS), which is caused by the functional loss of fragile X mental retardation protein (FMRP). However, the interaction between FMRP and lncRNAs on regulating neuronal development remains elusive. Here, we reported that FMRP directly interacted with lncRNA TUG1, and decreased its stability. Furthermore, TUG1 bond to transcriptional regulator, SnoN, and negatively modulated SnoN-Ccd1 pathway to specifically control axonal development. These observations suggested interplay between FMRP and lncRNAs might contribute to the pathogenesis of FXS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Dactinomycin / pharmacology
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism*
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Stability / drug effects
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism

Substances

  • Dixdc1 protein, mouse
  • Fmr1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Skil protein, mouse
  • long non-coding RNA TUG1, mouse
  • Fragile X Mental Retardation Protein
  • Dactinomycin