The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL

Area of Science:

• Molecular Biology
• Immunology
• Genomics

Background:

• Large intergenic noncoding RNAs (lincRNAs) are increasingly recognized for their regulatory roles in biological processes.
• The innate immune response involves complex gene regulation, including the production of key cytokines like TNFα.

Purpose of the Study:

• To identify lincRNAs involved in the innate immune response.
• To elucidate the function of a novel lincRNA, linc1992, in regulating TNFα expression and immune activation.
• To explore the potential role of this lincRNA in human inflammatory diseases.

Main Methods:

• Custom microarray analysis to identify differentially expressed lincRNAs in activated THP1 macrophages.
• RNA-binding assays to determine interactions between lincRNAs and proteins.
• Gene knockdown experiments to assess the functional role of lincRNAs in gene expression.
• Transcriptome analysis to identify downstream target genes.
• Correlation analysis with clinical data from Kawasaki disease patients.

Main Results:

• A panel of 159 lincRNAs was differentially expressed upon innate immune activation.
• linc1992 (renamed THRIL) was identified as essential for TNFα induction.
• THRIL specifically binds to hnRNPL, forming a complex that regulates TNFα promoter activity.
• THRIL is required for the expression of numerous immune-response genes, including other cytokines and regulators of TNFα.
• Knockdown of THRIL led to dysregulation of these genes during innate immune activation.
• THRIL expression levels correlated with symptom severity in Kawasaki disease patients.

Conclusions:

• lincRNAs, exemplified by THRIL, and their protein partners play critical roles in regulating TNFα expression.
• THRIL is a key regulator of the innate immune response.
• Dysregulation of THRIL may contribute to inflammatory diseases like Kawasaki disease.