CB27 - Investigating the role of SARS-CoV nonstructural protein 1 in the selective translation control of viral RNA
SCURS Disciplines
Biochemistry
Document Type
General Poster
Invited Presentation Choice
Not Applicable
Abstract
Nonstructural protein 1 (nsp1) from recent zoonotic coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV) functions as a host shutoff protein that stalls host mRNA translation and triggers their degradation, successfully suppressing host gene expression. In contrast, viral RNA selectively escapes the effects of the two-pronged suppression mechanism and continues the synthesis of viral proteins due to the presence of stem-loop 1 (SL1) in the viral leader sequence. Recent structural analysis of nsp1 bound to the 40S ribosomal subunit suggests that the flexible C-terminal region of nsp1 binds to the 40S ribosome at the mRNA binding site by folding into a well-defined alpha-turn-alpha structure; this interaction blocks host mRNAs from binding, stalling host mRNA translation. Meanwhile, the interaction between nsp1 and the viral leader sequence is thought to counteract that of nsp1-mediated translation suppression for the viral RNA. The exact nature of the selective control of translation has yet to be fully elucidated. Understanding these mechanisms more accurately is crucial to advance the current knowledge of similar host shutoff mechanisms in other viruses and to uncover new anti-viral targets to control the spread of such viruses.
Research in our laboratory is based on the hypothesis that the selective protection and preferential translation of viral RNA over host mRNA is based on nsp1’s ability to interact with RNA in both the nucleus and cytoplasm. To address this working hypothesis, we isolated and characterized the complexes formed between viral RNA, nsp1, and cellular extract using mass spectrometry, especially focusing on translational regulators that may aid nsp1 in differential selection of host mRNA for degradation. Using biotinylated SL1 to bind cytoplasmic proteins, we identified and tested its complex formation with CSDE1, eIF4G1, XRN2 and YBX1. Currently, we are investigating the binding of these proteins with mutated RNA and nsp1. Specifically, we are interested in CSDE1 (Cold Shock Domain Containing E1), which is an important factor in mRNA translation and stability.
Keywords
RNA, translation, sars coronavirus, host shutoff
Start Date
10-4-2026 9:30 AM
Location
University Readiness Center Greatroom
End Date
10-4-2026 11:30 AM
CB27 - Investigating the role of SARS-CoV nonstructural protein 1 in the selective translation control of viral RNA
University Readiness Center Greatroom
Nonstructural protein 1 (nsp1) from recent zoonotic coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV) functions as a host shutoff protein that stalls host mRNA translation and triggers their degradation, successfully suppressing host gene expression. In contrast, viral RNA selectively escapes the effects of the two-pronged suppression mechanism and continues the synthesis of viral proteins due to the presence of stem-loop 1 (SL1) in the viral leader sequence. Recent structural analysis of nsp1 bound to the 40S ribosomal subunit suggests that the flexible C-terminal region of nsp1 binds to the 40S ribosome at the mRNA binding site by folding into a well-defined alpha-turn-alpha structure; this interaction blocks host mRNAs from binding, stalling host mRNA translation. Meanwhile, the interaction between nsp1 and the viral leader sequence is thought to counteract that of nsp1-mediated translation suppression for the viral RNA. The exact nature of the selective control of translation has yet to be fully elucidated. Understanding these mechanisms more accurately is crucial to advance the current knowledge of similar host shutoff mechanisms in other viruses and to uncover new anti-viral targets to control the spread of such viruses.
Research in our laboratory is based on the hypothesis that the selective protection and preferential translation of viral RNA over host mRNA is based on nsp1’s ability to interact with RNA in both the nucleus and cytoplasm. To address this working hypothesis, we isolated and characterized the complexes formed between viral RNA, nsp1, and cellular extract using mass spectrometry, especially focusing on translational regulators that may aid nsp1 in differential selection of host mRNA for degradation. Using biotinylated SL1 to bind cytoplasmic proteins, we identified and tested its complex formation with CSDE1, eIF4G1, XRN2 and YBX1. Currently, we are investigating the binding of these proteins with mutated RNA and nsp1. Specifically, we are interested in CSDE1 (Cold Shock Domain Containing E1), which is an important factor in mRNA translation and stability.