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

• Published in: Journal of molecular biology Vol. 434; no. 7; p. 167469
• Main Authors: Chen, Geng, Yang, Yang, Wu, Qi-Jia, Cao, Liu, Ruan, Wen, Shao, Changwei, Jiang, Li, Tang, Peng, Ma, Suping, Jiang, Ao, Wang, Zhen, Wu, Kai, Zhang, Qiangfeng Cliff, Fu, Xiang-Dong, Zhou, Yu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 15.04.2022
• Subjects: antiviral response; biogenesis; DEAD Box Protein 58 - genetics; gene expression; Gene Expression Regulation; genes; HeLa Cells; Humans; ILF3; Interferon Type I - metabolism; interferons; interleukins; microprocessor; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA biogenesis; molecular biology; Nuclear Factor 90 Proteins - metabolism; Receptors, Immunologic - genetics; repeat-derived miRNAs; microprocessor; ILF3; miRNA biogenesis; repeat-derived miRNAs; antiviral response
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2022.167469

[Display omitted] •ILF3 represses many miRNAs or small RNAs identified via Spike-In small-RNA-seq.•ILF3 nuclear-CLIP-seq uncovers its RNA binding features in blocking Microprocessor.•ILF3 enhances anti-viral response via the ILF3/miR-582/RIG-I axis. MicroRNAs (miRNAs) play important roles in regulated gene expression and miRNA biogenesis is also subject to regulation, together constituting critical regulatory circuitries in numerous physiological and pathological processes. As a dsRNA binding protein, interleukin enhancer binding factor 3 (ILF3) has been implicated as a negative regulator in miRNA biogenesis, but the mechanism and specificity have remained undefined. Here, combining small-RNA-seq and CLIP-seq, we showed that ILF3 directly represses many miRNAs or perhaps other types of small RNAs annotated in both miRBase and MirGeneDB. We demonstrated that ILF3 preferentially binds to A/U-enriched motifs, which tend to lengthen and/or stabilize the stem-loop in pri-miRNAs, thereby effectively competing with the Microprocessor to block miRNA biogenesis. Focusing on the biological function of ILF3-suppressed miR-582-3p, we discovered that this LINE-derived miRNA targets a critical interferon-inducible gene RIG-I for repression, thus establishing a novel ILF3/miR-582/RIG-I axis in the antiviral response.