Page 6 - ebook

[A. Biochemistry/Molecular Biology] A-3

Regulation of replication-dependent histone mRNA decay via

site specific m⁶A modification

Jun Seok Hwang¹,² , Minkyung kim¹,² , Seung Hun Han¹,², Seongmin Jang¹,², Junho Choe¹,²*
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¹Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea, ²Research

Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea

Epitranscriptomics is a study of RNA modification in gene expression regulation that is currently receiving the

worldwide attention. In particular, N6-Methyladenosine (m⁶A) is the best characterized RNA modification that
exhibits the most prevalent RNA modification in the eukaryotic cells. Unlike the other eukaryotic mRNAs, histone

mRNAs exhibit several distinct features, including the absence of poly(A) tails and introns. Due to these
characteristics and experimental limitations, studies on m⁶A modifications of histone mRNA have been excluded

from most previous studies. Here, we show that m⁶A modification, like most other RNA species, also occurs in a
subset of replication-dependent histone mRNAs. We identified the proper regulation of m⁶A modification is critical

for the regulation of replication-dependent histone mRNA expression. Depletion of either METTL3 or ALKBH5
increases the histone mRNA half-life during the S phase of cell cycle. However, no significant change was found in

the translation efficiency of histone mRNA upon METTL3 or ALKBH5 knockdown. These findings uncover the
complexity of the molecular mechanism of m⁶A modification in histone mRNA expression and highlights the

essential role of m⁶A modification in cell cycle regulation.