ILF3 represses repeat-derived microRNAs targeting RIG-I mediated type I interferon response

Area of Science:

• Molecular Biology
• Gene Regulation
• RNA Biology

Background:

• MicroRNAs (miRNAs) are crucial regulators of gene expression, involved in various physiological and pathological processes.
• The biogenesis of miRNAs is tightly regulated, forming complex regulatory networks.
• Interleukin enhancer binding factor 3 (ILF3) is a double-stranded RNA (dsRNA) binding protein known to negatively regulate miRNA biogenesis, but its precise mechanism and specificity were unclear.

Purpose of the Study:

• To elucidate the mechanism and specificity by which ILF3 regulates miRNA biogenesis.
• To identify the small RNAs targeted by ILF3.
• To investigate the functional consequences of ILF3-mediated repression of specific miRNAs in biological processes.

Main Methods:

• Small-RNA sequencing (small-RNA-seq) to profile small RNA populations.
• Crosslinking immunoprecipitation sequencing (CLIP-seq) to identify ILF3 binding sites on RNA.
• Bioinformatic analysis of sequencing data to identify targeted miRNAs and binding motifs.
• Functional assays to assess the impact of miRNA regulation on gene expression and biological pathways.

Main Results:

• ILF3 directly represses the biogenesis of numerous miRNAs and potentially other small RNAs.
• ILF3 preferentially binds to AU-rich motifs within pri-miRNAs.
• Binding of ILF3 to AU-rich elements stabilizes pri-miRNA stem-loops, hindering Microprocessor complex access and blocking miRNA production.
• ILF3-suppressed miR-582-3p targets the interferon-inducible gene RIG-I, indicating a role in antiviral response.

Conclusions:

• ILF3 acts as a direct repressor of miRNA biogenesis through specific binding to pri-miRNA structures.
• The ILF3-mediated regulation of miRNA biogenesis influences cellular responses, exemplified by the novel ILF3/miR-582/RIG-I axis in antiviral immunity.