Abstract:
:Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological aging. Lamin C expression is mutually exclusive with the splicing of lamin A and progerin isoforms and occurs by alternative polyadenylation. Here, we investigate the function of lamin C in aging and metabolism using mice that express only this isoform. Intriguingly, these mice live longer, have decreased energy metabolism, increased weight gain, and reduced respiration. In contrast, progerin-expressing mice show increased energy metabolism and are lipodystrophic. Increased mitochondrial biogenesis is found in adipose tissue from HGPS-like mice, whereas lamin C-only mice have fewer mitochondria. Consistently, transcriptome analyses of adipose tissues from HGPS and lamin C-only mice reveal inversely correlated expression of key regulators of energy expenditure, including Pgc1a and Sfrp5. Our results demonstrate that LMNA encodes functionally distinct isoforms that have opposing effects on energy metabolism and lifespan in mammals.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Lopez-Mejia IC,de Toledo M,Chavey C,Lapasset L,Cavelier P,Lopez-Herrera C,Chebli K,Fort P,Beranger G,Fajas L,Amri EZ,Casas F,Tazi Jdoi
10.1002/embr.201338126subject
Has Abstractpub_date
2014-05-01 00:00:00pages
529-39issue
5eissn
1469-221Xissn
1469-3178pii
embr.201338126journal_volume
15pub_type
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