Recently, Professor Xu Tianjun’s Team at SHOU has made new progress in research on the regulation of the innate immune mechanism of fish via m6A methylation. The achievement has been published on iScience, a sub-journal of the Cell, under the title of FTO promotes innate immunity by controlling NOD1 expression via m6A-YTHDF2 manner in teleost (DOI: 10.1016/j.isci.2022.105646). Geng Shang, a doctoral candidate of SHOU, is the first author of this paper, and Professor Xu Tianjun is the corresponding author.
m6A is an epigenetic modification of eukaryote RNAs. More and more studies have shown that m6A plays an important role in regulating cell functions and biological processes, including mRNA metabolism, reproductive development, stem cell differentiation and reprogramming, and the circadian clock. However, the functions and action mechanisms of m6A modification in lower organisms remain unclear.
The fat mass and obesity-associated protein (FTO) has been proved to be a demethylase that can erase the m6A inside mRNAs. Taking fish (a category of lower organisms) as its research object, the research team found that FTO improves the ability of the fish body to resist viral and bacterial invasion in a way that depends on its demethylase activity. On the basis of the high-throughput sequencing results of MeRIP-seq, the research team anchored the target gene of FTO to NOD1, an important immune receptor in the NLR signaling pathway of fish, and discovered that FTO can erase the m6A modification of NOD1, thereby avoiding the degradation of NOD1 by m6A recognition protein YTHDF2 and ultimately enhancing the innate immunity and disease resistance of the fish body.
Molecular mechanism by which m6A regulates the NLR signaling pathway of fish
For a long time, the research team has conducted a series of studies on fish RNAs, and published dozens of original papers on the regulatory mechanisms of fish RNAs on internationally authoritative academic journals. This study for the first time elucidated the molecular regulatory mechanism of m6A modification in the innate immune process of fish, laying a foundation for disease prevention and control and immune interventions in fish.