Previous research has indicated that mitogen-activated protein kinases (MAPKs) play an important role in the regulation of mRNA stability by phosphorylating RNA-binding proteins. The researchers found that this was also the case for TNF-induced stabilization. The TNF-induced stabilization was MAPK-dependent and involved several genes with pathogenic potential, such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2. Thus, TNF appears to induce a late transcriptional program that leads to the expression of gene products that stabilize mRNAs in a selective manner. Because a stable transcript would theoretically be able to support continuously rising expression even in the presence of very low or decreasing rates of transcription, the stabilization of mRNA by TNF can explain the discordance in kinetics between active transcription and total mRNA expression in patients with RA. In this way, TNF contributes to enhanced expression of inflammatory genes and the perpetuation of synovitis.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
Reference
- Loupasakis K, Kuo D, Sokhi UK, et al. Tumor necrosis factor dynamically regulates the mRNA stabilome in rheumatoid arthritis fibroblast-like synoviocytes. PLoS One. 2017 Jul 14;12(7):e0179762. doi:10.1371/journal.pone.0179762. eCollection 2017.
