mRNA N6-methyladenosine methylation of postnatal liver development in pig

PLoS One. 2017 Mar 7;12(3):e0173421. doi: 10.1371/journal.pone.0173421. eCollection 2017.

Abstract

N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in the regulation of post-transcriptional protein coding gene expression. Liver is a vital organ and plays a major role in metabolism with numerous functions. Information concerning the dynamic patterns of mRNA m6A methylation during postnatal development of liver has been long overdue and elucidation of this information will benefit for further deciphering a multitude of functional outcomes of mRNA m6A methylation. Here, we profile transcriptome-wide m6A in porcine liver at three developmental stages: newborn (0 day), suckling (21 days) and adult (2 years). About 33% of transcribed genes were modified by m6A, with 1.33 to 1.42 m6A peaks per modified gene. m6A was distributed predominantly around stop codons. The consensus motif sequence RRm6ACH was observed in 78.90% of m6A peaks. A negative correlation (average Pearson's r = -0.45, P < 10-16) was found between levels of m6A methylation and gene expression. Functional enrichment analysis of genes consistently modified by m6A methylation at all three stages showed genes relevant to important functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. Genes with higher m6A methylation and lower expression levels at any particular stage were associated with the biological processes required for or unique to that stage. We suggest that differential m6A methylation may be important for the regulation of nutrient metabolism in porcine liver.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / metabolism
  • Animals
  • Computational Biology / methods
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Gene Ontology
  • Liver / growth & development*
  • Liver / metabolism*
  • Methylation
  • RNA / genetics*
  • RNA / metabolism*
  • Swine

Substances

  • RNA
  • Adenine
  • 6-methyladenine

Grants and funding

This work was supported by grants from the National High Technology Research and Development Program of China (863 Program) (2013AA102502), Sichuan Provincial Department of Science and Technology Program (2015JQO023), the National Natural Science Foundation of China (31530073, 31522055, 31472081 and 31401073), the National Program for Support of Top-notch Young Professionals, the Program for Innovative Research Team of Sichuan Province (2015TD0012), and the Fund of Fok Ying-Tung Education Foundation (141117). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.