Optimization of 5'UTR to evade SARS-CoV-2 Nonstructural protein 1-directed inhibition of protein synthesis in cells.

ABSTRACT: Maximizing the expression level of therapeutic proteins in cells is the general goal for DNA/mRNA therapies. It is particularly challenging to achieve efficient protein expression in the cellular contexts with inhibited translation machineries, such as in the presence of cellular Nonstructural protein 1 (Nsp1) of coronaviruses (CoVs) that has been reported to inhibit overall protein synthesis of host genes and exogenously delivered mRNAs/DNAs. In this study, we thoroughly examined the sequence and structure contexts of viral and non-viral 5'UTRs that determine the protein expression levels of exogenously delivered DNAs and mRNAs in cells expressing SARS-CoV-2 Nsp1. It was found that high 5'-proximal A/U content promotes an escape from Nsp1-directed inhibition of protein synthesis and resul

SUBMITTER: Chen SC 

PROVIDER: S-EPMC9968647 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature