A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA Stability Is Altered in Major Depression.

ABSTRACT: The serotonin-1A (5-HT1A) receptor is a key regulator of serotonergic activity and is implicated in mood and emotion. However, its post-transcriptional regulation has never been studied in humans. In the present study, we show that the "intronless" human 5-HT1A gene (HTR1A) is alternatively spliced in its 3'-UTR, yielding two novel splice variants. These variants lack a ∼1.6 kb intron, which contains an microRNA-135 (miR135) target site. Unlike the human HTR1A, the mouse HTR1A lacks the splice donor/accepter sites. Thus, in the mouse HTR1A, splicing was not detected. The two spliced mRNAs are extremely stable, are resistant to miR135-induced downregulation, and have greater translational output than the unspliced variant. Moreover, alternative HTR1A RNA s

SUBMITTER: Le Francois B 

PROVIDER: S-EPMC6596165 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature