# Interplay between coronaviruses and nonsense-mediated mRNA decay pathway

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $309,206

## Abstract

Coronaviruses (CoVs), which carry a large, single-stranded, positive-sense RNA genome, cause a variety of
diseases in humans and domestic animals. Human CoVs (HCoVs) usually infect the respiratory tract and
cause a range of symptoms varying from mild, such as the common cold, to more serious respiratory illnesses
like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), caused by two
highly pathogenic HCoVs, SARS-CoV and MERS-CoV. SARS-CoV caused a worldwide epidemic in 2002-
2003, resulting in more than 8,000 cases with an approximate mortality of 10%, while MERS-CoV emerged in
Saudi Arabia in 2012 and has been disseminated into other countries in the Middle East, North Africa, Europe,
and East Asia. HCoVs represent a major threat to public health and have the potential to cause a significant
negative economic impact. Currently, there are no approved vaccines and therapeutic agents against HCoVs.
The development of effective control measures against CoVs requires a comprehensive understanding of viral
gene expression strategies and host-CoV interactions. A plethora of studies have focused on investigating CoV
biology and have significantly contributed to our understanding of CoV replication mechanisms, including the
structure-function analyses of viral RNA elements as well as the viral proteins that are involved in viral
replication and assembly. However, there are still gaps in our knowledge of the post-transcriptional regulation
of viral gene expression, as only a limited number of studies have addressed this area of CoV research.
Particularly, very little is known about the cis-acting viral RNA elements and trans-acting host and viral factors
that regulate CoV mRNA transcript stability. One newly emerging research area in virology is understanding
interactions between viruses and host mRNA surveillance pathways that prevent generation/accumulation of
unwanted gene products. We have demonstrated that CoV mRNAs are the targets of the nonsense-mediated
mRNA decay (NMD) pathway, one of the host mRNA surveillance pathways, and that viral N protein protects
CoV mRNAs from NMD. Our data suggest the importance of N-mediated NMD suppression for efficient virus
replication. The present application will study the interplay between the NMD pathway and CoVs by testing the
following hypotheses: UPF1, the principal orchestrator of NMD, binds to the 3’ UTR of CoV mRNAs having
specific motifs, undergoes phosphorylation, and recruits SMG6, an endonuclease, leading to endonucleolytic
RNA cleavage; N binds to the 3’ UTRs of NMD targets and prevents an NMD factor(s) from accessing these
targets and/or N interacts with an NMD factor(s) and sequesters it away from the NMD pathway; and CoV
mutants having an increased susceptibility to NMD, cannot replicate as efficiently as the parental viruses. The
data obtained from these studies will provide mechanistic insights into NMD of CoV mRNAs and N-mediated
NMD pathway suppression, and wil...

## Key facts

- **NIH application ID:** 9972353
- **Project number:** 1R01AI146081-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Shinji Makino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,206
- **Award type:** 1
- **Project period:** 2020-03-11 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972353

## Citation

> US National Institutes of Health, RePORTER application 9972353, Interplay between coronaviruses and nonsense-mediated mRNA decay pathway (1R01AI146081-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972353. Licensed CC0.

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