Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Perturbation of Cellular Translation and RNA Metabolism by SARS-COV-2 Nucleoprotein Phase Separation

Award Number: R03AI159273
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 10/31/2023

Group Awards By:

View Award Description

Perturbation of Cellular Translation and RNA Metabolism by SARS-COV-2 Nucleoprotein Phase Separation - This proposal will investigate the role severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N protein phase separation in disrupting cellular translation and RNA metabolism. N protein phase separation creates membraneless organelles and concentrates RNAs in a droplet (dense) phase. While N protein is responsible for encapsidation of the viral genome, N protein also binds hundreds of host messenger RNAs, some of which are necessary for translation and nonsense-mediated decay (NMD). NMD targets diverse families of RNA viruses for RNA decay, including betacoronaviruses, and the N protein from Murine hepatitis virus (MHV) interferes with NMD during the early stages of infection. Since NMD targets 10% of cellular transcripts for degradation, inhibition by N protein likely has profound effects on the host cell transcriptome. While the mechanism underlying the inhibition of NMD by N protein remains unclear, phase separation and translational repression by N could be a predominant factor. The cellular proteins FUS and C9orf72 arginine- rich dipeptide repeats are known to phase separate, repress translation, inhibit NMD, and are associated with Amyotrophic lateral sclerosis (ALS) disease progression. Viral proteins, including N protein, may repress the translation of transcripts necessary for the co-translational NMD pathway, potentially shaping the host transcriptome in a way that favors virus replication. Recent work has shown that SARS-CoV-2 infection induces high expression of inflammatory cytokines but fails to mount a robust interferon response. The underlying factors driving these transcriptional responses remain unknown; however, N protein could provoke this response by interfering with NMD and blocking post-transcriptional regulation. This project will use transcriptome-wide ribosome profiling (Ribo-seq) to identify cellular transcripts that are translationally repressed by N protein. Previously identified NMD targets will be examined to determine if translational repression confers NMD-resistance. Phase-separation deficient N mutants will be expressed in parallel to determine whether phase separation is the driving force in translation and NMD inhibition. Finally, the results generated from this study will be cross-referenced with published RNA-seq datasets from SARS-CoV-2 infected cells to determine the extent that N protein contributes to the large-scale changes in gene expression during infection. These findings will better our understanding of the virus-host interactions that take place during SARS-CoV-2 infection and will support on-going vaccine and antiviral development, especially N-based approaches.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	2	6/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $78,250 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	5100 ROCKHILL RD	KANSAS CITY	MO	64110	JACKSON	USA	Allergy and Infectious Diseases Research	000	2	11/3/2022	NON-COMPETING CONTINUATION	$78,250
														Subtotal = $78,250

Issue Date FY: 2022 ( Subtotal = $78,250 )
2022	2022	UNIVERSITY OF MISSOURI SYSTEM	5100 ROCKHILL RD	KANSAS CITY	MO	64110	JACKSON	USA	Allergy and Infectious Diseases Research	000	1	10/28/2021	NEW	$78,250
														Subtotal = $78,250

Grand Total All Awards = $156,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Perturbation of Cellular Translation and RNA Metabolism by SARS-COV-2 Nucleoprotein Phase Separation

Award Number: R03AI159273

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 10/31/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer