title: Identification and expression of a novel transcript of the growth and differentiation factor-11 gene.
abstract: 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.
authors.affiliation: AgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand, frank.jeanplong@gmail.com.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Jeanplong
authors.forename: Shelley J
authors.initials: SJ
authors.lastname: Falconer
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Oldham
authors.forename: Nauman J
authors.initials: NJ
authors.lastname: Maqbool
authors.forename: Mark
authors.initials: M
authors.lastname: Thomas
authors.forename: Alex
authors.initials: A
authors.lastname: Hennebry
authors.forename: Christopher D
authors.initials: CD
authors.lastname: McMahon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055412:Growth Differentiation Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics* / Q000302:isolation & purification; D062085:RNA, Long Noncoding / Q000235:genetics*; D017385:Sequence Homology
chemical_list: D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors; D020033:Protein Isoforms; D062085:RNA, Long Noncoding