Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK

Yone Jung Yoon, Morgan C. McKenna, David A. Rollins, Minseok Song, Tal Nuriel, Steven S. Gross, Guoqiang Xu, Charles E. Glatt

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 Srcfamily 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.

Original languageEnglish
Pages (from-to)11624-11629
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number28
DOIs
StatePublished - 9 Jul 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK'. Together they form a unique fingerprint.

Cite this