The role of alternative polyadenylation in the antiviral innate immune response

• Published in: Nature communications Vol. 8; no. 1; p. 14605
• Main Authors: Jia, Xin, Yuan, Shaochun, Wang, Yao, Fu, Yonggui, Ge, Yong, Ge, Yutong, Lan, Xihong, Feng, Yuchao, Qiu, Feifei, Li, Peiyi, Chen, Shangwu, Xu, Anlong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/89; 13/95; 3' Untranslated Regions - genetics; 38/39; 38/43; 38/90; 38/91; 631/250/2502; 631/337/572; 82/1; Animals; Down-Regulation; Female; Gene expression; Gene Expression Regulation - immunology; Humanities and Social Sciences; Humans; Immunity, Innate - genetics; Infections; Interferon; Leukocytes, Mononuclear; Macrophages; Mice; Mice, Inbred C57BL; multidisciplinary; Polyadenylation - immunology; Primary Cell Culture; Proteins; Receptors, Pattern Recognition - immunology; Science; Science (multidisciplinary); Signal Transduction - immunology; Vesicular stomatitis Indiana virus - immunology; Viral infections; Virus Diseases - immunology; Beijing China; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14605

Alternative polyadenylation (APA) is an important regulatory mechanism of gene functions in many biological processes. However, the extent of 3′ UTR variation and the function of APA during the innate antiviral immune response are unclear. Here, we show genome-wide poly(A) sites switch and average 3′ UTR length shortens gradually in response to vesicular stomatitis virus (VSV) infection in macrophages. Genes with APA and mRNA abundance change are enriched in immune-related categories such as the Toll-like receptor, RIG-I-like receptor, JAK-STAT and apoptosis-related signalling pathways. The expression of 3′ processing factors is down-regulated upon VSV infection. When the core 3′ processing factors are knocked down, viral replication is affected. Thus, our study reports the annotation of genes with APA in antiviral immunity and highlights the roles of 3′ processing factors on 3′ UTR variation upon viral infection. RNA processing by alternative polyadenylation (APA) can result in 3′UTR diversity and regulation of target RNA function. Here the authors survey APA in viral infection of macrophages.