# The Emerging Role of METTL3 in Lung Diseases

## TL;DR

This paper reviews how METTL3, an enzyme involved in RNA modification, plays a key role in various lung diseases and could be a promising target for new therapies.

## Contribution

The paper provides a comprehensive review of METTL3's role in lung diseases and highlights its potential as a novel therapeutic target.

## Key findings

- METTL3 influences mRNA metabolism and is linked to the progression of lung diseases like asthma and COPD.
- Emerging evidence connects METTL3 to lung cancer and other respiratory conditions through m6A-dependent regulation.
- Targeting METTL3 shows promise as a therapeutic strategy, though more research is needed for clinical translation.

## Abstract

N6-methyladenosine (m6A) represents the most abundant and tightly controlled modification within eukaryotic mRNA, critically influencing RNA metabolism and function. The m6A methyltransferase Like-3 (METTL3), responsible for the complex’s catalytic function, has emerged as a central epitranscriptomic regulator governing mRNA stability, alternative splicing, nuclear export, and the efficiency of mRNA translation. Converging research shows that METTL3 is involved in the pathogenesis of numerous disorders via m6A-dependent, post-transcriptional regulation of gene programs controlling cell growth, migration, and immune pathways. Regarding pulmonary pathophysiology, METTL3-mediated m6A is tied to disease initiation and progression in conditions such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung infections, acute respiratory distress syndrome (ARDS). This review summarizes the contemporary evidence for METTL3’s roles and regulatory network in diverse pulmonary pathologies. We further highlight emerging strategies for targeting METTL3 as a potential therapeutic approach, underscoring its promise as a novel epitranscriptomic target. Beyond inflammatory and fibrotic disorders, we also summarize emerging evidence linking METTL3 to lung cancer and briefly outline other respiratory conditions (e.g., ILD, bronchiectasis, and secondary pulmonary hypertension), highlighting common translational themes and remaining gaps. Further studies are required to clarify the disease-specific and context-dependent actions of METTL3 and to advance the clinical translation of m6A-based therapies.