ILF3 represses repeat-derived microRNAs targeting RIG-I mediated type I interferon response. Issue 7 (15th April 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of molecular biology. Volume 434:Issue 7(2022)
• Publication Date: 2022-04-15
• Subjects: ILF3 -- miRNA biogenesis -- repeat-derived miRNAs -- microprocessor -- antiviral response; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2022.167469
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: 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. Abstract: 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.