4.8 Article

Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.756288

Keywords

COVID-19; alternative polyadenylation; immunity; alternative splicing; APA regulator

Categories

Funding

  1. China Postdoctoral Science Foundation [2020M683623XB]
  2. 64th Batch of the China Postdoctoral Science Foundation [2018M643382]
  3. Young Scientists Fund of the Guangxi Natural Science Foundation [2018GXNSFBA281014]
  4. Guangxi Bagui Scholar
  5. Guangxi Medical University Training Program for Distinguished Young Scholars
  6. Guangxi Science Fund for Distinguished Young Scholars [2018GXNSFFA281001]
  7. National Natural Science Foundation of China [82160389]

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The study found that genes with APA in COVID-19 patients were enriched in gene ontology categories related to innate immunity, and APA events may provide better predictions than AS. This suggests that APA could act as a potential therapeutic target and novel biomarker in COVID-19 patients.
The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.

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