Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha.
The transcriptional co-activator PGC-1alpha 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-1alpha (NT-PGC-1alpha) produced by alternative 3' splicing that introduces an in-frame stop codon into PGC-1alpha mRNA. The expressed protein includes the first 267 amino acids of PGC-1alpha and 3 additional amino acids from the splicing insert. NT-PGC-1alpha 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-1alpha are dynamically regulated in the context of physiological signals that regulate full-length PGC-1alpha, 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-1alpha is a co-expressed, previously unrecognized form of PGC-1alpha with functions that are both unique from and complementary to PGC-1alpha.
Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
Yubin
Y
Zhang
Peter
P
Huypens
Aaron W
AW
Adamson
Ji Suk
JS
Chang
Tara M
TM
Henagan
Anik
A
Boudreau
Natalie R
NR
Lenard
David
D
Burk
Johannes
J
Klein
Nina
N
Perwitz
Jeho
J
Shin
Mathias
M
Fasshauer
Anastasia
A
Kralli
Thomas W
TW
Gettys
D017667:Adipocytes / Q000166:cytology; D017398:Alternative Splicing; D000818:Animals; D018388:Codon, Terminator; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D025941:Protein Interaction Mapping; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D015533:Transcriptional Activation
D018388:Codon, Terminator; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors