Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1α

Yubin Zhang, Peter Huypens, Aaron W. Adamson, Ji Suk Chang, Tara M. Henagan, Anik Boudreau, Natalie R. Lenard, David Burk, Johannes Klein, Nina Perwitz, Jeho Shin, Mathias Fasshauer, Anastasia Kralli, Thomas W. Gettys*

*Korrespondierende/r Autor/-in für diese Arbeit
90 Zitate (Scopus)

Abstract

The transcriptional co-activator PGC-1α regulates functional plasticity in adipose tissue by linking sympathetic input to the transcriptional program of adaptive thermogenesis. We report here a novel truncated form of PGC-1α(NT-PGC-1α) produced by alternative 3′ splicing that introduces an in-frame stop codon into PGC-1α mRNA. The expressed protein includes the first 267 amino acids of PGC-1α and 3 additional amino acids from the splicing insert. NT-PGC-1α contains the transactivation and nuclear receptor interaction domains but is missing key domains involved in nuclear localization, interaction with other transcription factors, and protein degradation. Expression and subcellular localization of NT-PGC-1α are dynamically regulated in the context of physiological signals that regulate full-length PGC-1α, but the truncated domain structure conveys unique properties with respect to protein-protein interactions, protein stability, and recruitment to target gene promoters. Therefore, NT-PGC-1α is a co-expressed, previously unrecognized form of PGC-1α with functions that are both unique from and complementary to PGC-1α.

OriginalspracheEnglisch
ZeitschriftJournal of Biological Chemistry
Jahrgang284
Ausgabenummer47
Seiten (von - bis)32813-32826
Seitenumfang14
ISSN0021-9258
DOIs
PublikationsstatusVeröffentlicht - 20.11.2009

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

  • 201-03 Zellbiologie

Fingerprint

Untersuchen Sie die Forschungsthemen von „Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1α“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren