METTL14 Regulates Intestine Cellular Senescence Through MA Modification of Lamin B Receptor

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2022 Dec 29

PMID 36578521

Authors

Zizhen Zhang

Meng Xue

Jingyu Chen

Zhuo Wang

Fangyu Ju

Jiaojiao Ni

Jiawei Sun

Haoyue Wu

Huimei Zheng

Ziwei Lou

Yawen Zhang

Xiaohang Yang

Shujie Chen

Yongmei Xi

Liangjing Wang

Affiliations

Soon will be listed here.

Abstract

N-6-Methyladenosine (mA) modification is involved in multiple biological processes including aging. However, the regulation of mA methyltransferase-like 14 (METTL14) in aging remains unclear. Here, we revealed that the level of mA modification and the expression of METTL14 were particularly decreased in the intestine of aged mice as compared to young mice. Similar results were confirmed in . Knockdown of Mettl14 in resulted in a short lifespan, associated disrupted intestinal integrity, and reduced climbing ability. In human CCD-18Co cells, knockdown of METTL14 accelerated cellular senescence, and the overexpression of METTL14 rescued senescent phenotypes. We also identified the lamin B receptor (LBR) as a target gene for METTL14-mediated mA modification. Knockdown of METTL14 decreased mA level of LBR, resulted in LBR mRNA instability, and thus induced cellular senescence. Our findings suggest that METTL14 plays an essential role in the mA modification-dependent aging process via the regulation of LBR and provides a potential target for cellular senescence.

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