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Cited by 122RNA Research and Splicinginterferon and immune responsesRNA regulation and disease

The role of alternative polyadenylation in the antiviral innate immune response

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Jia, Xin, Yuan, Shaochun, Wang, Yao, Fu, Yonggui, Ge, Yong, Ge, Yutong, Lan, Xihong, Feng, Yuchao +4 more·2017·Nature Communications
DOI 10.1038/ncomms14605PMC PMC5333124
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Abstract

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.

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  • In macrophages, the antiviral innate immune response leads to alternative polyadenylation resulting in 3'UTR shortening and loss of microRNA binding sites.

    “Assessing the influence of microRNAs on their target may be more difficult in the setting of the antiviral innate immune response, as it was proven for macrophages that this leads to alternative polyadenylation resulting in 3′UTR shortening and loss of microRNA binding sites [42].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [42]

    The Results sections on transcriptome-wide analysis and 3′ UTR variation report that VSV-infected human and mouse macrophages undergo poly(A)-site switching and average 3′ UTR shortening (pages not provided). But the Results section on APA and viral replication says selected genes *may* escape miRNA binding when short 3′ UTRs are used; it does not establish loss of microRNA binding sites as a proven outcome. It also cautions that the relevant processing-factor changes may not be controlled by the innate antiviral pathway. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Jia, X., Yuan, S., Wang, Y., Fu, Y., Ge, Y., Ge, Y., Lan, X., Feng, Y., Qiu, F., Li, P., Chen, S., & Xu, A.
Affiliations
Sun Yat-sen University (CN)
Corresponding author
Xu, Anlong
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-02-24
Volume
8
Issue
1
Pages
14605-14605
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms14605
PMC
PMC5333124
OpenAlex
W2590031594
Cited by
122
References
5
Citations by year
2026: 14 · 2025: 18 · 2024: 10 · 2023: 18 · 2022: 14 · 2021: 17 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 4
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31470846, 31270018, 91231206, 81430099)
  • Guangzhou Municipal Science and Technology Bureau (201607020037)
  • National Key Research and Development Program of China (2013CB835303, 81430099)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
alternative polyadenylation, poly(A) site, antiviral innate immunity, vesicular stomatitis virus, macrophages, Toll-like receptor signaling, JAK/STAT signaling, apoptosis, viral replication, mRNA levels
MeSH terms
Animals, Female, Gene Expression Regulation, Humans, Immunity, Innate, Leukocytes, Mononuclear, Macrophages, Mice, Inbred C57BL, Vesicular stomatitis Indiana virus, Virus Diseases, Signal Transduction, Down-Regulation, 3' Untranslated Regions, Polyadenylation, Receptors, Pattern Recognition, Mice, Primary Cell Culture

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