Review Volume 15, Issue 24 pp 15676—15700
Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis
- 1 Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
- 2 Medical Experimental Center, General Hospital of Ningxia Medical University, Yinchuan 750000, Ningxia, China
- 3 School of Clinical Medicine, Ningxia Medical University, Yinchuan 750000, Ningxia, China
Received: July 16, 2023 Accepted: October 23, 2023 Published: December 18, 2023
https://doi.org/10.18632/aging.205312How to Cite
Copyright: © 2023 Bi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is characterized by high morbidity and mortality and one of the major diseases that seriously hang over global human health. Autophagy is a crucial regulator in the complicated pathophysiological processes of sepsis. The activation of autophagy is known to be of great significance for protecting sepsis induced organ dysfunction. Recent research has demonstrated that N6-methyladenosine (m6A) methylation is a well-known post-transcriptional RNA modification that controls epigenetic and gene expression as well as a number of biological processes in sepsis. In addition, m6A affects the stability, export, splicing and translation of transcripts involved in the autophagic process. Although it has been suggested that m6A methylation regulates the biological metabolic processes of autophagy and is more frequently seen in the progression of sepsis pathogenesis, the underlying molecular mechanisms of m6A-modified autophagy in sepsis have not been thoroughly elucidated. The present article fills this gap by providing an epigenetic review of the processes of m6A-modified autophagy in sepsis and its potential role in the development of novel therapeutics.
Abbreviations
m6A: N6-methyladenosine; ICU: intensive care unit; mRNA: messenger RNAs; rRNA: ribosomal RNAs; snRNA: small nuclear RNAs; IGFBPs: insulin-like growth factor 2 mRNA binding proteins; MAT2A: methionine adenosyltransferase 2A; METTL16: methyltransferase-like 16; SAM: S-adenosylmethionine; METTL3: methyltransferase-like 3; METTL14: methyltransferase-like 14; METTL5: methyltransferase-like 5; WTAP: Wilms tumor 1-associated protein; VIRMA: Vir-like m6A methyltransferase associated; RBM15: RNA binding motif protein 15; ZCCHC4: zinc-finger CCHC domain-containing protein 4; FTO: fat mass and obesity-related proteins; ALKBH5: alkB homolog 5; YTHDF 1-3: YTH structural domain family 1-3; YTHDC 1-2: YTH structural domain containing family 1-2; eIF3: eukaryotic translation initiation factor 3 subunit A; IGF2BP1/2/3: insulin-like growth factor 2 mRNA binding protein 1/2/3; HNRNPA2/B1: heterogeneous nuclear ribonucleoprotein A2/B1; MAC: m6A-METTL complex; MACOM: m6A-METTL-associated complex; NAOX: nucleic acid oxygenase; SOX2: SRY (sex determining region Y)-box 2; piRNA: Piwi-interacting RNA; CHAPIR: cardiac-hypertrophy-associated piRNA; HR: hazard ratio; LPS: lipopolysaccharide; ARDS: acute respiratory distress syndrome; TFEB: Transcription factor EB; PPM1A: protein phosphatase 1A; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2; TP53INP2: tumor protein p53 inducible nuclear protein 2; TMA7: translation machinery associated 7 homolog; ATF4: activating transcription factor 4.