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

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.

authors

Yoon Y,McKenna MC,Rollins DA,Song M,Nuriel T,Gross SS,Xu G,Glatt CE

doi

10.1073/pnas.1301485110

subject

Has Abstract

pub_date

2013-07-09 00:00:00

pages

11624-9

issue

28

eissn

0027-8424

issn

1091-6490

pii

1301485110

journal_volume

110

pub_type

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