Nonstructural protein 1 widespread RNA decay phenotype varies among coronaviruses

Extensive remodeling of host gene expression by nonstructural protein 1 (nsp1) of coronaviruses is a well-documented and conserved aspect of coronavirus-host takeover. Using comparative transcriptomics we investigated the diversity of transcriptional targets between various nsp1 proteins. Additionally, affinity purification followed by mass spectrometry was implemented to identify common interactors between the different nsp1 proteins. Although we detected widespread RNA destabilization, closely related nsp1 showed little similarities in clustering of targeted genes. We observed a partial overlap in transcriptional targeting between α-CoV 229E and MERS nsp1, which may suggest a common targeting mechanism, as MERS nsp1 preferentially targets nuclear transcripts. Our interactome data show great variability between nsp1 interactions, with 229E nsp1, the smallest nsp1 tested here, interacting with the most number of host proteins. Although nsp1 is a rather well-conserved protein with conserved functions across different coronaviruses, our data indicate that its precise effects on the host cell are virus specific.