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Frontiers in Cell and Developmental Biology
Article . 2021 . Peer-reviewed
License: CC BY
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Other literature type . 2021
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N6 -Methyladenosine Negatively Regulates Human Respiratory Syncytial Virus Replication

Authors: Fabian Figueroa; Alonso Vega-Gibson; Joseline Catrileo; Aracelly Gaete-Argel; Aracelly Gaete-Argel; Sebastian Riquelme-Barrios; Sebastian Riquelme-Barrios; +9 Authors

N6 -Methyladenosine Negatively Regulates Human Respiratory Syncytial Virus Replication

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification described in eukaryotic mRNA and several viral RNA including human respiratory syncytial virus (HRSV). Here, we evaluated the impact of m6A writers, erasers and readers on HRSV genomic RNA accumulation and inclusion bodies assembly during viral replication. We observed that the METTL3/METTL14 m6A writer complex plays a negative role in HRSV protein synthesis and viral titers, while m6A erasers FTO and ALKBH5 had the opposite effect. We also observed that m6A readers YTHDF1-3 bind to the viral genomic RNA inducing a decrease in its intracellular levels and thus, inhibiting viral replication. Finally, we observed that overexpression of YTHDFs proteins caused a decrease in the size of inclusion bodies (IBs), accompanied by an increase in their number. METTL3 knockdown cells showed an opposite effect indicating that the dynamics of IBs assembly and coalescence are strongly affected by m6A readers in a mechanism dependent on m6A writers. Taken together, our results demonstrated that the m6A modification negatively affects HRSV replication, possibly through a mechanism involving the assembly of inclusion bodies, the main factories of viral genomic RNA synthesis.

Country
Chile
Keywords

gRNA synthesis, Inclusion bodies, N6-methyladenosine, QH301-705.5, N6 -methyladenosine, inclusion bodies, RNA modification, Cell and Developmental Biology, Human respiratory syncytial virus, Viral replication, viral replication, Biology (General), human respiratory syncytial virus

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Top 10%
Average
Top 10%
Green
gold