TIGP (BIO)—mRNA Signatures in Gene Expression Control: Lessons Learned from Biased Codon Usage and SARS-CoV-2 Nsp1-Mediated Translational Repression

Abstract

Understanding the principles of gene expression control in normal or stress condition will solve the fundamental question of how an organism’s genotype leads to its phenotype as well as discover solutions to counteract the stresses. Here I will share two of our recent findings that mRNA sequence features regulate gene expression at the level of post-transcription in normal condition (1), and at the level of translation in the presence of translation repressor, SARS-CoV-2 Nsp1 protein (2). Specifically, we discovered that, in human cells, the codon bias-mediated gene expression control initiates from the nucleus. Genes with poor codons are selectively degraded by nuclear RNA degradation after synthesis. In addition, our data support there existed a sequence-position effect and cell-type specificity of this regulation. The other discovery is the identification of a sequence rule to escape SARS-CoV-2 Nsp1 mediated translational suppression. Although it was thought the stem-loop 1 structure of SARS-CoV-2 5’UTR is the key to escape its Nsp1 suppression, we surprisingly found the specific sequence context, rather than the formation of RNA structures, is the key determinant to escape Nsp1 translational suppression. The biology and following application will be further discussed.

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