The RNA binding protein HuR determines the differential translation of autism-associated FoxP subfamily members in the developing neocortex

Sci Rep. 2016 Jul 7:6:28998. doi: 10.1038/srep28998.

Abstract

Forkhead-box domain (Fox) containing family members are known to play a role in neocorticogenesis and have also been associated with disorders on the autism spectrum. Here we show that a single RNA-binding protein, Hu antigen R (HuR), dictates translation specificity of bound mRNAs and is sufficient to define distinct Foxp-characterized subpopulations of neocortical projection neurons. Furthermore, distinct phosphorylation states of HuR differentially regulate translation of Foxp mRNAs in vitro. This demonstrates the importance of RNA binding proteins within the framework of the developing brain and further confirms the role of mRNA translation in autism pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Autism Spectrum Disorder / genetics
  • Chromatin Immunoprecipitation
  • ELAV-Like Protein 1 / physiology*
  • Female
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / genetics
  • Gestational Age
  • Male
  • Mice
  • Neocortex / embryology
  • Neocortex / metabolism*
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neurogenesis / genetics*
  • Phosphorylation
  • Protein Biosynthesis*
  • Protein Processing, Post-Translational
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics

Substances

  • 3' Untranslated Regions
  • ELAV-Like Protein 1
  • Elavl1 protein, mouse
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Foxp2 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Repressor Proteins