PUM2 binds SARS-CoV-2 RNA and PUM1 mildly reduces viral RNA levels, but neither protein affects progeny virus production
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Updated: Jan 6, 2026
MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Nhi Phan1, Yelizaveta Zaytseva1, Chia-Ching Lin1,2
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Abstract:
Pumilio proteins (PUM1 and PUM2) are essential post-transcriptional regulators of gene expression found across plants, animals and yeast. They bind Pumilio response elements (PREs) on messenger RNAs (mRNAs) to modulate mRNA stability and translation. PUMs have been implicated in diverse cellular processes, including stem cell maintenance, neurogenesis and cell cycle regulation. They have also been reported to negatively regulate innate immunity genes and to participate in viral RNA sensing. Previous high-throughput interactome studies revealed that PUMs bind severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. We found that SARS-CoV-2 transcripts contain multiple conserved PREs, some of which are preferentially bound by PUM2. Surprisingly, altering PUM levels does not affect the production of progeny virions. However, depletion of PUM1 slightly increases intracellular viral RNA levels, suggesting that PUM1 either plays a mild antiviral role against SARS-CoV-2 or regulates host factors that promote viral replication. Notably, PUM1 also negatively regulates innate immunity gene expression both at steady state and during SARS-CoV-2 infection. Our findings support a complex immunomodulatory role for PUM1, acting both as a negative regulator of innate immunity genes and a mild inhibitor of SARS-CoV-2 RNA accumulation. However, in cell culture, these roles appear negligible based on viral progeny output. Whether the multiple PREs found in the SARS-CoV-2 genome contribute to evasion of PUM1 activity remains an open question.
Insights
Pumilio proteins (PUM1 and PUM2) regulate gene expression and interact with SARS-CoV-2 RNA. While PUM1 shows mild antiviral activity and regulates immunity, its impact on viral production is negligible in cell culture.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Pumilio proteins (PUM1, PUM2) are key post-transcriptional regulators controlling mRNA stability and translation via Pumilio response elements (PREs).
- PUMs are involved in vital cellular functions and have known roles in regulating innate immunity and viral RNA sensing.
- Previous studies identified PUM protein binding to SARS-CoV-2 RNA.
Purpose of the Study:
- To investigate the interaction between Pumilio proteins and SARS-CoV-2 RNA.
- To determine the functional impact of PUM1 and PUM2 on SARS-CoV-2 replication and host innate immunity.
Main Methods:
- Analysis of conserved PREs within SARS-CoV-2 transcripts.
- Assessment of PUM protein binding preferences to viral RNA.
- Evaluation of viral progeny production upon alteration of PUM protein levels.
- Measurement of intracellular viral RNA levels.
- Examination of PUM1's effect on innate immunity gene expression during infection.
Main Results:
- SARS-CoV-2 transcripts contain multiple conserved PREs, with PUM2 showing preferential binding to some.
- Altering PUM protein levels did not significantly affect progeny virion production.
- Depletion of PUM1 led to a slight increase in intracellular viral RNA, suggesting a mild antiviral role.
- PUM1 was confirmed as a negative regulator of innate immunity genes, both basally and during SARS-CoV-2 infection.
Conclusions:
- PUM1 exhibits a dual role: a mild inhibitor of SARS-CoV-2 RNA accumulation and a negative regulator of innate immunity.
- Despite these roles, PUM1's influence on viral progeny output in cell culture appears minimal.
- The presence of multiple PREs in the SARS-CoV-2 genome may facilitate viral evasion of PUM1-mediated restriction.
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