dc.contributor.author
Grohmann, Maik
dc.contributor.author
Hammer, Paul
dc.contributor.author
Walther, Maria
dc.contributor.author
Paulmann, Nils
dc.contributor.author
Büttner, Andreas
dc.contributor.author
Eisenmenger, Wolfgang
dc.contributor.author
Baghai, Thomas C.
dc.contributor.author
Schüle, Cornelius
dc.contributor.author
Rupprecht, Rainer
dc.contributor.author
Bader, Michael
dc.contributor.author
Bondy, Brigitta
dc.contributor.author
Zill, Peter
dc.contributor.author
Priller, Josef
dc.contributor.author
Walther, Diego J.
dc.date.accessioned
2018-06-08T11:06:48Z
dc.date.available
2015-11-23T11:34:35.047Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21638
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24926
dc.description.abstract
Brain serotonin (5-HT) neurotransmission plays a key role in the regulation of
mood and has been implicated in a variety of neuropsychiatric conditions.
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis
of 5-HT. Recently, we discovered a second TPH isoform (TPH2) in vertebrates,
including man, which is predominantly expressed in brain, while the previously
known TPH isoform (TPH1) is primarly a non-neuronal enzyme. Overwhelming
evidence now points to TPH2 as a candidate gene for 5-HT-related psychiatric
disorders. To assess the role of TPH2 gene variability in the etiology of
psychiatric diseases we performed cDNA sequence analysis of TPH2 transcripts
from human post mortem amygdala samples obtained from individuals with
psychiatric disorders (drug abuse, schizophrenia, suicide) and controls. Here
we show that TPH2 exists in two alternatively spliced variants in the coding
region, denoted TPH2a and TPH2b. Moreover, we found evidence that the pre-
mRNAs of both splice variants are dynamically RNA-edited in a mutually
exclusive manner. Kinetic studies with cell lines expressing recombinant TPH2
variants revealed a higher activity of the novel TPH2B protein compared with
the previously known TPH2A, whereas RNA editing was shown to inhibit the
enzymatic activity of both TPH2 splice variants. Therefore, our results
strongly suggest a complex fine-tuning of central nervous system 5-HT
biosynthesis by TPH2 alternative splicing and RNA editing. Finally, we present
molecular and large-scale linkage data evidencing that deregulated alternative
splicing and RNA editing is involved in the etiology of psychiatric diseases,
such as suicidal behaviour.
en
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/de/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Alternative Splicing and Extensive RNA Editing of Human TPH2 Transcripts
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 5 (2010), 1, Artikel Nr. e8956
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0008956
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008956
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000023510
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005698
dcterms.accessRights.openaire
open access