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Updated: Sep 15, 2025
MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
PUM2 binds SARS-CoV-2 RNA and PUM1 mildly reduces viral RNA levels, but neither protein affects progeny virus
Nhi Phan1, Yelizaveta Zaytseva1, Chia-Ching Lin1
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 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 a host factor that promotes 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. While PUM1 shows mild antiviral activity against SARS-CoV-2 RNA, neither protein impacts viral progeny production in cell culture.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Pumilio proteins (PUM1, PUM2) are key post-transcriptional regulators binding Pumilio Response Elements (PREs) on mRNAs.
- PUMs influence stem cell maintenance, neurogenesis, and innate immunity, and interact with viral RNAs.
- Previous studies indicated PUMs bind SARS-CoV-2 RNA.
Purpose of the Study:
- To investigate the role of PUM1 and PUM2 in SARS-CoV-2 infection.
- To determine if PUM proteins affect viral RNA levels and progeny production.
- To elucidate PUM1's function in regulating innate immunity during viral infection.
Main Methods:
- Analysis of SARS-CoV-2 transcripts for conserved PREs.
- Assessment of PUM1 and PUM2 binding to viral RNA.
- Manipulation of PUM protein levels to observe effects on viral RNA and progeny.
- Measurement of innate immunity gene expression.
Main Results:
- SARS-CoV-2 transcripts contain multiple conserved PREs, with PUM2 showing preferential binding.
- Altering PUM levels did not affect SARS-CoV-2 progeny virion production.
- PUM1 depletion slightly increased intracellular viral RNA levels.
- PUM1 was confirmed as a negative regulator of innate immunity genes, both basally and during infection.
Conclusions:
- PUM1 exhibits a complex immunomodulatory role, negatively regulating innate immunity and mildly inhibiting SARS-CoV-2 RNA accumulation.
- The identified PREs in the SARS-CoV-2 genome may facilitate evasion of PUM1's antiviral activity.
- Despite observed effects on viral RNA and immunity, PUM roles appear negligible for viral output in cell culture.
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