# Transcriptional Regulation of WTAP Isoforms by NF-κB Signaling in Human Monocytes

## TL;DR

This study shows how the NF-κB signaling pathway controls the expression of different WTAP isoforms in human monocytes during immune activation.

## Contribution

The paper reveals a new NF-κB-dependent mechanism for regulating WTAP isoform expression in monocytes.

## Key findings

- WTAP expression in monocytes increases after LPS stimulation through alternative promoter usage.
- RELA (NF-κB) directly regulates the promoter-specific induction of WTAP isoforms.
- Both WTAP isoforms produce the same protein, indicating transcriptional regulation.

## Abstract

N6-methyladenosine (m6A) is a dynamic RNA modification that critically modulates gene expression in immune responses. While m6A regulators such as WTAP are implicated in inflammatory and autoimmune diseases, the mechanisms governing their expression during innate immune activation remain unclear. Here, we demonstrate that WTAP expression in human CD14+ monocytes is upregulated upon lipopolysaccharide (LPS) stimulation and is associated with alternative promoter usage leading to distinct mRNA isoforms. Bioinformatic analysis and pharmacological inhibition reveal that the transcription factor RELA (NF-κB pathway) directly contributes to this promoter-specific induction. Functional analyses show that both WTAP isoforms encode identical proteins, indicating transcriptional, rather than post-transcriptional, regulation. These findings uncover a novel NF-κB-dependent mechanism regulating WTAP isoform expression in activated monocytes, providing insight into the epitranscriptomic modulation of inflammation and potential dysregulation in autoimmune disease.