Skip to main content
Log in

Novel alternatively spliced isoforms of MEF2A and their mRNA expression patterns in pigs

  • Research Article
  • Published:
Journal of Genetics Aims and scope Submit manuscript

Abstract

The present study aimed to identify the alternatively spliced isoforms of pig MEF2A gene and to determine their mRNA expression patterns. Four alternatively spliced isoforms of pig MEF2A gene (i.e. MEF2A1, MEF2A2, MEF2A3 and MEF2A4) were cloned according to the results of transcriptome sequencing. The fifth to eighth exons of MEF2A1 were normally spliced. In MEF2A2, the fifth exon was missing; the sixth exon had an extra 138 bp at its \(5^\prime \) end, and the seventh exon had an extra 102 bp at its \(3^{\prime }\) end. In MEF2A3, the fifth exon was missing, and the sixth exon had an additional 138 bp at its \(5^\prime \) end. In MEF2A4, the seventh exon had an extra 102 bp at its \(3^{\prime }\) end. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that the expression profiles of the four alternatively spliced transcripts in the longissimus dorsi differed between the Mashen and Large White pigs. MEF2A1 and MEF2A2 expression levels were the highest at 90 days of age and lowest at 180 days of age. MEF2A3 and MEF2A4 expression levels increased with age (in days). The four alternatively spliced isoforms of MEF2A were also expressed in the small intestine, cerebellum, pancreas, heart and lung. The discovery of new alternatively spliced transcripts of the MEF2A gene may be utilized in understanding its biological functions.

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

Access this article

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
Fig. 8

Similar content being viewed by others

References

  • Akhtar M. W., Kim M. S., Adachi M., Morris M. J., Qi X., Richardson J. A. et al. 2012 In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival. PLoS One 7, e34863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen F. Y., Feng L. I., Sen-Ya A. N., Niu H., Chu Q. X., Wang Z. F. et al. 2013 Cloning of cattle MEF2A gene and construction of its eukaryotic expression vector. Chin. J. Anim. Vet. Sci. 44, 140–144.

    CAS  Google Scholar 

  • Chen L., Cheng B., Li L., Zhan S., Wang L., Zhong T. et al. 2015 The molecular characterization and temporal-spatial expression of myocyte enhancer factor 2 genes in the goat and their association with myofiber traits. Gene 555, 223–230.

    Article  CAS  PubMed  Google Scholar 

  • de Klerk E. and t Hoen P. A. 2015 Alternative mRNA transcription, processing, and translation: insights from RNA sequencing. Trends Genet. 31, 128–139.

  • Ewen E. P., Snyder C. M., Wilson M., Desjardins D. and Naya F. J. 2011 The Mef2A transcription factor coordinately regulates a costamere gene program in cardiac muscle. J. Biol. Chem. 286, 29644–29653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Excoffon K. J., Bowers J. R. and Sharma P. 2014 Alternative splicing of viral receptors: a review of the diverse morphologies and physiologies of adenoviral receptors. Recent Res. Dev. Virol. 9, 1–24.

    PubMed  PubMed Central  Google Scholar 

  • Ghosh S. and Chan C. K. 2016 Analysis of RNA-seq data using TopHat and cufflinks. Methods Mol. Biol. 1374, 339–361.

    Article  CAS  PubMed  Google Scholar 

  • Gilbert W. 1978 Why genes in pieces? Nature 271, 501.

    Article  CAS  PubMed  Google Scholar 

  • Graveley B. R., Brooks A. N., Carlson J. W., Duff M. O., Landolin J. M., Yang L. et al. 2011 The developmental transcriptome of Drosophila melanogaster. Nature 471, 473–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamid F. M. and Makeyev E. V. 2014 Emerging functions of alternative splicing coupled with nonsense-mediated decay. Biochem. Soc. Trans. 42, 1168–1173.

    Article  CAS  PubMed  Google Scholar 

  • Linseman D. A., Cornejo B. J., Le S. S., Meintzer M. K., Laessig T. A., Bouchard R. J. et al. 2003 A myocyte enhancer factor 2D (MEF2D) kinase activated during neuronal apoptosis is a novel target inhibited by lithium. J. Neurochem. 85, 1488–1499.

    Article  CAS  PubMed  Google Scholar 

  • Maimon A., Mogilevsky M., Shilo A., Golan-Gerstl R., Obiedat A., Ben-Hur V. et al. 2014 Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras-induced transformation. Cell Rep. 7, 501–513.

    Article  CAS  PubMed  Google Scholar 

  • Marquez Y., Brown J. W., Simpson C., Barta A. and Kalyna M. 2012 Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis. Genome Res. 22, 1184–1195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin J. F., Miano J. M., Hustad C. M., Copeland N. G., Jenkins N. A. and Olson E. N. 1994 A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing. Mol. Cell. Biol. 14, 1647–1656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKinsey T. A., Zhang C. L. and Olson E. N. 2002 MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem. Sci. 27, 40–47.

    Article  CAS  PubMed  Google Scholar 

  • Molkentin J. D., Black B. L., Martin J. F. and Olson E. N. 1995 Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 83, 1125–1136.

    Article  CAS  PubMed  Google Scholar 

  • Molkentin J. D., Black B. L., Martin J. F. and Olson E. N. 1996 Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C. Mol. Cell Biol. 16, 2627–2636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mortazavi A., Williams B. A., McCue K., Schaeffer L. and Wold B. 2008 Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5, 621–628.

    Article  CAS  PubMed  Google Scholar 

  • Naya F. J., Black B. L., Wu H., Bassel-Duby R., Richardson J. A., Hill J. A. et al. 2002 Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat. Med. 8, 1303–1309.

    Article  CAS  PubMed  Google Scholar 

  • Snyder C. M., Rice A. L., Estrella N. L., Held A., Kandarian S. C. and Naya F. J. 2013 MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in skeletal muscle regeneration. Development 140, 31–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trapnell C., Pachter L. and Salzberg S. L. 2009 TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D. Z., Valdez M. R., McAnally J., Richardson J. and Olson E. N. 2001 The Mef2c gene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development. Development. 128, 4623–4633.

    CAS  PubMed  Google Scholar 

  • Wang J., Ye Z., Huang T. H., Shi H. and Jin V. X. 2017 Computational methods and correlation of exon-skipping events with splicing, transcription, and epigenetic factors. Methods Mol. Biol. 1513, 163–170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan-Xia Q. I., Zhang X. H., Pang Y. Z., Wang Y. Q. and Liao H. 2012 Expression patterns of MyoD and MEF2 genes during the development of Nanyang cattle longissimus dorsi muscle. J. Henan Agric. Univ. 46, 558–561.

    Google Scholar 

  • Zhang D. J., Gao Z. S., Di L. and Yang G. W. 2009 Cloning and expression of the porcine MEF2a gene. Chin. J. Anim. Vet. Sci. 36, 55–59.

    Google Scholar 

  • Zhang M., Zhu B. and Davie J. 2015 Alternative splicing of MEF2C pre-mRNA controls its activity in normal myogenesis and promotes tumorigenicity in rhabdomyosarcoma cells. J. Biol. Chem. 290, 310–324.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Shanxi Science and Technology Committee (grant nos. 201605D131045-24 and 201705D131028-19) and the San Jin Scholars Programme of China (2016 and 2017). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this paper. Thanks to all the staff of the Datong pig farm.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bu Gao Li.

Additional information

Corresponding editor: Silvia Garagna

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, X.H., Zhang, Q., Li, M. et al. Novel alternatively spliced isoforms of MEF2A and their mRNA expression patterns in pigs. J Genet 97, 977–985 (2018). https://doi.org/10.1007/s12041-018-0990-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12041-018-0990-0

Keywords

Navigation