Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. McPherron AC, Lawler AM, Lee SJ (1999) Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 22:260–264. doi:10.1038/10320

    Article  PubMed  CAS  Google Scholar 

  2. Nakashima M, Toyono T, Akamine A, Joyner A (1999) Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta superfamily during mouse embryogenesis. Mech Dev 80:185–189

    Article  PubMed  CAS  Google Scholar 

  3. Gamer LW, Wolfman NM, Celeste AJ, Hattersley G, Hewick R, Rosen V (1999) A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. Dev Biol 208:222–232. doi:10.1006/dbio.1998.9191

    Article  PubMed  CAS  Google Scholar 

  4. Gamer LW, Cox KA, Small C, Rosen V (2001) Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. Dev Biol 229:407–420. doi:10.1006/dbio.2000.9981

    Article  PubMed  CAS  Google Scholar 

  5. Xing F, Tan X, Zhang PJ, Ma J, Zhang Y, Xu P, Xu Y (2007) Characterization of amphioxus GDF8/11 gene, an archetype of vertebrate MSTN and GDF11. Dev Genes Evol 217:549–554. doi:10.1007/s00427-007-0162-3

    Article  PubMed  CAS  Google Scholar 

  6. Jeanplong F, Falconer SJ, Thomas M, Matthews KG, Oldham JM, Watson T, McMahon CD (2012) Growth and differentiation factor-11 is developmentally regulated in skeletal muscle and inhibits myoblast differentiation. Open J Mol Integr Physiol 2:127–138. doi:10.4236/ojmip.2012.24018

    Article  Google Scholar 

  7. McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83–90. doi:10.1038/387083a0

    Article  PubMed  CAS  Google Scholar 

  8. Lee SJ, McPherron AC (2001) Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 98:9306–9311. doi:10.1073/pnas.151270098

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Rebbapragada A, Benchabane H, Wrana JL, Celeste AJ, Attisano L (2003) Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Mol Cell Biol 23:7230–7242

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Oh SP, Yeo CY, Lee Y, Schrewe H, Whitman M, Li E (2002) Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning. Genes Dev 16:2749–2754. doi:10.1101/gad.1021802

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, Wright JF, Barker C, Ehrmantraut G, Holmstrom J, Trowell B, Gertz B, Jiang MS, Sebald SM, Matzuk M, Li E, Liang LF, Quattlebaum E, Stotish RL, Wolfman NM (2005) Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA 102:18117–18122. doi:10.1073/pnas.0505996102

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Covi JA, Kim HW, Mykles DL (2008) Expression of alternatively spliced transcripts for a myostatin-like protein in the blackback land crab, Gecarcinus lateralis. Comp Biochem Physiol A 150:423–430. doi:10.1016/j.cbpa.2008.04.608

    Article  CAS  Google Scholar 

  13. Castelhano-Barbosa EC, Gabriel JE, Alvares LE, Monteiro-Vitorello CB, Coutinho LL (2005) Temporal and spatial expression of the myostatin gene during chicken embryo development. Growth Dev Aging 69:3–12

    PubMed  CAS  Google Scholar 

  14. Huang KL, Wang JW, Han CC, Liu HH, Li L, Dai F, Pan Z, Xu F, He H, Xu H (2011) Developmental expression and alternative splicing of the duck myostatin gene. Comp Biochem Physiol Part D Genomics Proteomics 6:238–243. doi:10.1016/j.cbd.2011.04.002

    Article  PubMed  CAS  Google Scholar 

  15. Garikipati DK, Gahr SA, Roalson EH, Rodgers BD (2007) Characterization of rainbow trout myostatin-2 genes (rtMSTN-2a and -2b): genomic organization, differential expression, and pseudogenization. Endocrinology 148:2106–2115. doi:10.1210/en.2006-1299

    Article  PubMed  CAS  Google Scholar 

  16. Jeanplong F, Falconer SJ, Oldham JM, Thomas M, Gray TS, Hennebry A, Matthews KG, Kemp FC, Patel K, Berry C, Nicholas G, McMahon CD (2013) Discovery of a mammalian splice variant of myostatin that stimulates myogenesis. PLoS ONE 8:e81713. doi:10.1371/journal.pone.0081713

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Lundby C, Nordsborg N, Kusuhara K, Kristensen KM, Neufer PD, Pilegaard H (2005) Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies. Eur J Appl Physiol 95:351–360. doi:10.1007/s00421-005-0022-7

    Article  PubMed  CAS  Google Scholar 

  18. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  19. Tukey JW (1953) Some selected quick and easy methods of statistical analysis. Trans N Y Acad Sci 16:88–97

    Article  PubMed  CAS  Google Scholar 

  20. Oldham JM, Osepchook CC, Jeanplong F, Falconer SJ, Matthews KG, Conaglen JV, Gerrard DF, Smith HK, Wilkins RJ, Bass JJ, McMahon CD (2009) The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone. J Physiol 587:669–677. doi:10.1113/jphysiol.2008.161521

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Lee TI, Young RA (2000) Transcription of eukaryotic protein-coding genes. Annu Rev Genet 34:77–137. doi:10.1146/annurev.genet.34.1.77

    Article  PubMed  CAS  Google Scholar 

  23. Funkenstein B, Olekh E (2010) Growth/differentiation factor-11: an evolutionary conserved growth factor in vertebrates. Dev Genes Evol 220:129–137. doi:10.1007/s00427-010-0334-4

    Article  PubMed  CAS  Google Scholar 

  24. Esquela AF, Lee SJ (2003) Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 257:356–370

    Article  PubMed  CAS  Google Scholar 

  25. McPherron AC, Huynh TV, Lee SJ (2009) Redundancy of myostatin and growth/differentiation factor 11 function. BMC Dev Biol 9:24. doi:10.1186/1471-213X-9-24

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Dinger ME, Pang KC, Mercer TR, Mattick JS (2008) Differentiating protein-coding and noncoding RNA: challenges and ambiguities. PLoS Comput Biol 4:e1000176. doi:10.1371/journal.pcbi.1000176

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Kapranov P, St Laurent G, Raz T, Ozsolak F, Reynolds CP, Sorensen PH, Reaman G, Milos P, Arceci RJ, Thompson JF, Triche TJ (2010) The majority of total nuclear-encoded non-ribosomal RNA in a human cell is ‘dark matter’ un-annotated RNA. BMC Biol 8:149. doi:10.1186/1741-7007-8-149

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. St Laurent G, Savva YA, Kapranov P (2012) Dark matter RNA: an intelligent scaffold for the dynamic regulation of the nuclear information landscape. Front Genet 3:57. doi:10.3389/fgene.2012.00057

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43:904–914. doi:10.1016/j.molcel.2011.08.018

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. St Laurent G, Shtokalo D, Tackett MR, Yang Z, Eremina T, Wahlestedt C, Urcuqui-Inchima S, Seilheimer B, McCaffrey TA, Kapranov P (2012) Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells. BMC Genom 13:504. doi:10.1186/1471-2164-13-504

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Neil Cox for his help with statistical analysis. We also thank Linda Tseng for technical assistance, and Drs Christine Couldrey and Adrian Molenaar for critically reading the manuscript. This study was supported by a research grant (C10X0703) from the Foundation of Research Science and Technology, New Zealand.

Conflict of interest

Authors declare no competing financial interests.

Data deposition

All novel DNA sequences were deposited to GenBank under the following accession numbers: KC561772, KC561773 and KC561774.

Author information

Authors and Affiliations

  1. AgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand

    Ferenc Jeanplong, Shelley J. Falconer, Jenny M. Oldham, Nauman J. Maqbool, Mark Thomas, Alex Hennebry & Christopher D. McMahon

Authors
  1. Ferenc Jeanplong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shelley J. Falconer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jenny M. Oldham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nauman J. Maqbool
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alex Hennebry
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher D. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ferenc Jeanplong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jeanplong, F., Falconer, S.J., Oldham, J.M. et al. Identification and expression of a novel transcript of the growth and differentiation factor-11 gene. Mol Cell Biochem 390, 9–18 (2014). https://doi.org/10.1007/s11010-013-1949-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1949-3

Keywords

Search

Navigation