METTL16 regulates m6A methylation on chronic hepatitis B associated gene HLA-DPB1 involved in liver fibrosis

• Published in: Frontiers in genetics Vol. 13; p. 996245
• Main Authors: Gao, Haibing, Wang, Xiangmei, Ma, Huaxi, Lin, Shenglong, Zhang, Dongqing, Wu, Wenjun, Liao, Ziyuan, Chen, Mengyun, Li, Qin, Lin, Minghua, Li, Dongliang
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 04-11-2022
• Subjects: CHB (chronic hepatitis B); Genetics; GWAS; HBV-hepatitis B virus; M6A; METTL16
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2022.996245

The role of genetic factors in the occurrence and progression of CHB (CHB) is still not fully explored. In recent years, genome-wide association studies on CHB patients have demonstrated that a large number of CHB-associated single nucleotide polymorphisms exist in the gene intron, which may regulate expression at the transcriptional level. Modification of RNA m
6
A methylation is one of the key mechanisms regulating gene expression. Here we show that
METTL16
, an m
6
A regulator involved in mRNA intron splicing, is differentially expressed in CHB the tissue of patients who has definite diagnosis of mild and severe fibrosis. At the same time, there are also significant differences in the expression of CHB-associated genes such as
HLA-DPA1
and
HLA-DPB1
. The expression of
HLA-DPB1
is related to
METTL16
. Furthermore, analyses of RNA binding of METTL16 and
HLA-DPB1
show that the silencing of
METTL16
in astrocytes downregulates m
6
A and expression of HLA-DPB1. In conclusion,
METTL16
participates in the progression of CHB fibrosis by regulating the m
6
A level and expression of HLA-DPB1.