Identification and expression of a novel transcript of the growth and differentiation factor-11 gene

Mol Cell Biochem. 2014 May;390(1-2):9-18. doi: 10.1007/s11010-013-1949-3. Epub 2013 Dec 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Proteins / biosynthesis*
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / isolation & purification
  • Cloning, Molecular
  • DNA, Complementary
  • Female
  • Gene Expression Regulation, Developmental
  • Growth Differentiation Factors / biosynthesis*
  • Growth Differentiation Factors / genetics*
  • Growth Differentiation Factors / isolation & purification
  • Male
  • Mice
  • Molecular Sequence Data
  • Organ Specificity
  • Protein Isoforms / genetics*
  • Protein Isoforms / isolation & purification
  • RNA, Long Noncoding / genetics*
  • Sequence Homology

Substances

  • Bone Morphogenetic Proteins
  • DNA, Complementary
  • Gdf11 protein, mouse
  • Growth Differentiation Factors
  • Protein Isoforms
  • RNA, Long Noncoding

Associated data

  • GENBANK/KC561772
  • GENBANK/KC561773
  • GENBANK/KC561774