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Mol Cell Biochem ; 390(1-2): 9-18, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24378996

RESUMO

The growth and differentiation factor-11 (GDF-11) gene is thought to code for a single protein that plays a crucial role in regulating the development of multiple tissues. In this study, we aimed to investigate if the GDF-11 gene has another transcript and, if so, to characterise this transcript and determine its tissue-specific and developmental expression. We have identified a novel transcript of GDF-11 in mouse muscle, which contains the 3' region of intron 1, exon 2, exon 3 and 3'UTR, and has two transcription initiation sites and a single termination site. We named the novel transcript GDF-11ΔEx1 because it does not contain exon 1 of canonical GDF-11. The GDF-11ΔEx1 transcript was expressed in the skeletal muscles, heart, brain and kidney, but was undetectable in the liver and gut. The concentration of the GDF-11ΔEx1 transcript was increased in gastrocnemius muscles from three to 6 weeks of age, a period of accelerated muscle growth, steadily declined thereafter and was higher in male than female mice (P < 0.001 for age and sex). GDF-11ΔEx1 cDNA was predicted to code for a putative N-terminal-truncated propeptide and the canonical ligand for GDF-11. However, propeptide-specific antibodies could not identify proteins of the expected size in skeletal muscle. Interestingly, in silico analysis of the GDF-11ΔEx1 RNA predicted a secondary structure with the potential to coordinate multiple protein interactions as a molecular scaffold. Therefore, we postulate that GDF-11ΔEx1 may act as a long non-coding RNA to regulate the transcription of canonical GDF-11 and/or other genes in skeletal muscle and other tissues.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Proteínas Morfogenéticas Ósseas/genética , Fatores de Diferenciação de Crescimento/biossíntese , Fatores de Diferenciação de Crescimento/genética , Isoformas de Proteínas/genética , RNA Longo não Codificante/genética , Sequência de Aminoácidos , Animais , Proteínas Morfogenéticas Ósseas/isolamento & purificação , Clonagem Molecular , DNA Complementar , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Diferenciação de Crescimento/isolamento & purificação , Masculino , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos , Isoformas de Proteínas/isolamento & purificação , Homologia de Sequência
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