The placental epitranscriptome: post-transcriptional m6A modification at 5’ UTR may relate fetal growth

The 2017 Meeting of the International Federation of Placenta Associations

Manchester Central

August 31, 2017

P1.32

Poster presentation

The placental epitranscriptome: post-transcriptional m6A modification at 5’ UTR may relate fetal growth

Kosuke Taniguchi1,2, Tomoko Kawai2, Kazuhiko Nakabayashi2, Haruhiko Sago3, Kohji Okamura4, Jo Kitawaki1, Kenichiro Hata2
1Dept. Obstet. Gynecol., Kyoto Pref. Univ. Med., Japan, 2Dept. Matern.-Fetal Biol., NCCHD, Japan, 3Ctr. Matern.-Fetal, Neonatal and Reprod. Med., NCCHD, Japan, 4Dept. Sys. BioMed., NCCHD, Japan

Objectives: Recent studies have revealed several kinds of post-transcriptional modifications. N6-methyladenosine (m6A), one of these modifications, is known to exist abundantly in mRNAs and regulates their fate, suggesting to be related to many diseases. The placenta has been reported to be characterized by global DNA hypomethylation. This may suggest that placental gene expression is fine-tuned by special steps after transcription. Therefore we hypothesized that post-transcriptional m6A modification may also play important roles in fetal growth through placental functions.
Methods: We carried out Methylated RNA immunoprecipitation followed by sequencing on human placental tissues (6 cases of appropriate-for-date (AFD), 7 of small-for-date (SFD), and 5 of heavy-for-date (HFD)). Among these groups, we compared amount of m6A modification in two genomic regions; 5’ UTR and the vicinity of stop codon, which are suggested to be important m6A functional targets.
Results: Unsupervised hierarchical clustering of placental transcripts based on m6A modification at 5’ UTR tended to classify phenotypes of fetal growth, while the amount of these transcripts did not relate to fetal growth categories. Next, we performed Mann-Whitney U test to detect transcripts relating to fetal growth through m6A modification. Between AFD and SFD, 92 and 193 transcripts were differentially modified by m6A at 5’ UTR and in the vicinity of stop codon, respectively. Similarly, 91 transcripts and 369 transcripts had significantly different m6A modifica- tions at each region between AFD and HFD. Intriguingly, almost all (95 to 97%) of these transcripts existed at the same level between clinical categories.
Conclusion: Some sort of genes exhibited equal transcriptional amount but different m6A modifications. These genes might regulate fetal growth through altering placental functions dependent on post-transcriptional modification, especially at 5’ UTR.