Heterogeneous nuclear ribonucleoprotein (hnRNP) F is a novel component of oligodendroglial RNA transport granules contributing to regulation of myelin basic protein (MBP) synthesis

J Biol Chem. 2012 Jan 13;287(3):1742-54. doi: 10.1074/jbc.M111.235010. Epub 2011 Nov 29.

Abstract

Myelin basic protein (MBP) is a major component of central nervous system (CNS) myelin. The absence of MBP results in the loss of almost all compact myelin in the CNS. MBP mRNA is sorted into RNA granules that are transported to the periphery of oligodendrocytes in a translationally inactive state. A central mediator of this transport process is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 that binds to the cis-acting A2-response element in the 3'UTR of MBP mRNA. Recently, we found that activation of the Src family nonreceptor tyrosine kinase Fyn in oligodendrocytes leads to phosphorylation of hnRNP A2 and to increased translation of MBP mRNA. Here, we identify the RNA-binding protein hnRNP F as a novel component of MBP mRNA transport granules. It is associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures and is involved in post-transcriptional regulation of MBP expression. Fyn kinase activity results in phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules. Our results define hnRNP F as a regulatory element of MBP expression in oligodendrocytes and imply an important function of hnRNP F in the control of myelin synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / physiology
  • Animals
  • Biological Transport / physiology
  • Cells, Cultured
  • Cytoplasmic Granules / genetics
  • Cytoplasmic Granules / metabolism*
  • Gene Expression Regulation / physiology*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism*
  • Humans
  • Mice
  • Myelin Basic Protein / biosynthesis*
  • Myelin Basic Protein / genetics
  • Myelin Sheath / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Proto-Oncogene Proteins c-fyn / genetics
  • Proto-Oncogene Proteins c-fyn / metabolism

Substances

  • 3' Untranslated Regions
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H
  • Myelin Basic Protein
  • hnRNP A2
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn