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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 32813-32826 |
| Number of pages | 14 |
| Journal | Journal of Biological Chemistry |
| Volume | 284 |
| Issue number | 47 |
| DOIs | |
| State | Published - Nov 20 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1α. / Zhang, Yubin; Huypens, Peter; Adamson, Aaron W.; Chang, Ji Suk; Henagan, Tara M.; Boudreau, Anik; Lenard, Natalie R.; Burk, David; Klein, Johannes; Perwitz, Nina; Shin, Jeho; Fasshauer, Mathias; Kralli, Anastasia; Gettys, Thomas W.
In: Journal of Biological Chemistry, Vol. 284, No. 47, 20.11.2009, p. 32813-32826.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1α
AU - Zhang, Yubin
AU - Huypens, Peter
AU - Adamson, Aaron W.
AU - Chang, Ji Suk
AU - Henagan, Tara M.
AU - Boudreau, Anik
AU - Lenard, Natalie R.
AU - Burk, David
AU - Klein, Johannes
AU - Perwitz, Nina
AU - Shin, Jeho
AU - Fasshauer, Mathias
AU - Kralli, Anastasia
AU - Gettys, Thomas W.
PY - 2009/11/20
Y1 - 2009/11/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70450252013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70450252013&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.037556
DO - 10.1074/jbc.M109.037556
M3 - Article
C2 - 19773550
AN - SCOPUS:70450252013
VL - 284
SP - 32813
EP - 32826
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 47
ER -