Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK Academic Article uri icon

Overview

MeSH Major

  • Anxiety
  • Poly A
  • Protein Biosynthesis
  • RNA, Messenger
  • Ribonucleoproteins
  • Serotonin Plasma Membrane Transport Proteins

abstract

  • The serotonin transporter (SERT) is a major regulator of serotonergic neurotransmission and anxiety-related behaviors. SERT is expressed in two alternative polyadenylation forms that differ by an evolutionarily conserved element in the 3' untranslated region of its mRNA. Expression of SERT mRNA containing the distal polyadenylation element is associated with decreased anxiety-related behaviors in mice and humans, suggesting that this element has behaviorally relevant modulatory effects on SERT expression. We have identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a protein known to integrate multiple signal transduction pathways with gene expression, as a SERT distal polyadenylation element binding protein. This interaction is functionally meaningful because genetic manipulation of hnRNPK alters expression of the SERT protein. Furthermore, the trophic factor S100β induces Src-family kinase-mediated tyrosine phosphorylation of hnRNPK and increased SERT expression. These results identify a previously unknown mechanism of regulated SERT expression and provide a putative mechanism by which the SERT distal polyadenylation element modulates anxiety-related behaviors.

publication date

  • July 9, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3710847

Digital Object Identifier (DOI)

  • 10.1073/pnas.1301485110

PubMed ID

  • 23798440

Additional Document Info

start page

  • 11624

end page

  • 9

volume

  • 110

number

  • 28