Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection

Abstract

Circular RNAs (circRNAs) generated via back-splicing are enhanced by flanking complementary sequences. Expression levels of circRNAs vary under different conditions, suggesting participation of protein factors in their biogenesis. Using genome-wide siRNA screening that targets all human unique genes and an efficient circRNA expression reporter, we identify double-stranded RNA-binding domain containing immune factors NF90/NF110 as key regulators in circRNA biogenesis. NF90/NF110 promote circRNA production in the nucleus by associating with intronic RNA pairs juxtaposing the circRNA-forming exon(s); they also interact with mature circRNAs in the cytoplasm. Upon viral infection, circRNA expression is decreased, in part owing to the nuclear export of NF90/NF110 to the cytoplasm. Meanwhile, NF90/NF110 released from circRNP complexes bind to viral mRNAs as part of their functions in antiviral immune response. Our results therefore implicate a coordinated regulation of circRNA biogenesis and function by NF90/NF110 in viral infection.

The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells

“…Biotin-coupled circRNA and miRNA capture Biotin-coupled miRNA and circRNA pull-down assays were performed as described previously [11,12]. Briefly, 3′ end biotinylated circRNA-ACAP2 (digoxin-5′-TCACACAGGCAGCTTTGGAAGAAG-3′-Digoxin; RiboBio, Guangzhou, China) was transfected into SW480 cells at a final concentration of 20 nM for 1 day.…”

The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting

“…It has instead been suggested that circular RNAs may help form large RNA-protein complexes, e.g. at neuronal synapses (Rybak-Wolf et al, 2015; You et al, 2015), be translated (Abe et al, 2015; Chen and Sarnow, 1995; Kramer et al, 2015; Legnini et al, 2017; Pamudurti et al, 2017; Yang et al, 2017), or be involved in innate immune responses (Chen et al, 2017; Li et al, 2017). …”

Antiviral Immunity and Circular RNA: No End in Sight

“…These proteins include pattern recognition receptors, such as RIG-I, MDA5, and TLR3, which couple viral dsRNA binding to antiviral cytokine production, and effector molecules, such as PKR, ADAR1, and NF90/110, which upon dsRNA binding induce a variety of changes in cellular and viral RNA processes to suppress viral replication. The two reports by Chen et al (2017) and Li et al (2017) in this issue of Molecular Cell suggest circular RNAs (circRNAs), derived from both host and viruses, as a new class of RNA molecules that interact with these dsRNA binding antiviral proteins and interface the host-virus interaction.…”

“…The report by Li et al (2017) provides a related, but somewhat different, perspective of how the antiviral innate immune system interacts with circRNAs. Unlike in Chen et al (2017)’s paper, which focuses on how viral circRNAs affect the host immune function, Li et al (2017) report how the host immune system and viral infection affect host circRNA biogenesis.…”

“…Unlike in Chen et al (2017)’s paper, which focuses on how viral circRNAs affect the host immune function, Li et al (2017) report how the host immune system and viral infection affect host circRNA biogenesis. Li et al (2017) used a genome-wide short hairpin RNA (shRNA) library screening to identify genes involved in host circRNA biogenesis. Intriguingly, many of the viral RNA receptor genes, including RIG-I and NF90/110, were identified as important factors for circRNA generation.…”