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  • Epitranscriptomic profiling in human placenta: N6-methyladenosine modification at the 5'-untranslated region is related to fetal growth and preeclampsia.

Epitranscriptomic profiling in human placenta: N6-methyladenosine modification at the 5'-untranslated region is related to fetal growth and preeclampsia.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2020-01-10)
Kosuke Taniguchi, Tomoko Kawai, Jo Kitawaki, Junko Tomikawa, Kazuhiko Nakabayashi, Kohji Okamura, Haruhiko Sago, Kenichiro Hata
ABSTRACT

Intracellular mRNA levels are not always proportional to their respective protein levels, especially in the placenta. This discrepancy may be attributed to various factors including post-transcriptional regulation, such as mRNA methylation (N6-methyladenosine: m6A). Here, we conducted a comprehensive m6A analysis of human placental tissue from neonates with various birth weights to clarify the involvement of m6A in placental biology. The augmented m6A levels at the 5'-untranslated region (UTR) in mRNAs of small-for-date placenta samples were dominant compared to reduction of m6A levels, whereas a decrease in m6A in the vicinity of stop codons was common in heavy-for-date placenta samples. Notably, most of these genes showed similar expression levels between the different birth weight categories. In particular, preeclampsia placenta samples showed consistently upregulated SMPD1 protein levels and increased m6A at 5'-UTR but did not show increased mRNA levels. Mutagenesis of adenosines at 5'-UTR of SMPD1 mRNAs actually decreased protein levels in luciferase assay. Collectively, our findings suggest that m6A both at the 5'-UTR and in the vicinity of stop codon in placental mRNA may play important roles in fetal growth and disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mechlorethamine hydrochloride, 98%
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
(1R,2S,5R)-(−)-Menthol, ReagentPlus®, 99%
Sigma-Aldrich
N6-Methyladenosine 5′-monophosphate sodium salt, ≥97% (HPLC)