The International Journal of Neuropsychopharmacology

Research Article

miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells

Pablo R. Moyaa1 c1, Jens R. Wendlanda2, Jennifer Salemmea1, Ruby L. Frieda1 and Dennis L. Murphya1

a1 Laboratory of Clinical Science, NIMH Intramural Research Program, NIH, Bethesda, MD, USA

a2 Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Abstract

The serotonin transporter (SERT) is a key regulatory molecule in serotonergic transmission implicated in numerous biological processes relevant to human disorders. Recently, it was shown that SERT expression is controlled by miR-16 in mouse brain. Here, we show that SERT expression is regulated additionally by miR-15a as well as miR-16 in human and rat tissues. This post-transcriptional regulation was observed and characterized in reporter assays and likewise when endogenous SERT expression was evaluated in human placental choriocarcinoma JAR cells and rat brain raphe RN46A cells – two cell lines that endogenously express SERT. Similar effects for miR-16 to those of miR-15a were found in both human and rat cell lines. The effects of miR-15a and miR-16 were comparable in extent to those originally reported for miR-16 in mice. These findings represent a novel layer of complexity for SERT expression regulation exerted by the mir-15a/16 cluster, whose genes are adjacently located at human chromosome 13q14.3.

(Received November 02 2011)

(Reviewed December 12 2011)

(Revised March 30 2012)

(Accepted April 01 2012)

(Online publication May 08 2012)

Key words

  • miR-15a;
  • miR-16;
  • serotonin transporter;
  • SERT;
  • SLC6A4

Correspondence

c1 Address for correspondence: P. R. Moya, PhD, Laboratory of Clinical Science, National Institute of Mental Health, 10/3D41, 10 Center Dr, Bethesda, MD 20892, USA. Tel.: 301 5940126 Fax: 301 4020188 Email: moyap@mail.nih.gov