A zinc finger-containing papain-like protease couples subgenomic mRNA synthesis to genome translation in a positive-stranded RNA virus

The genome expression of positive-stranded RNA viruses starts with translat ion rather than transcription. For some viruses, the genome is the only vir al mRNA and expression is regulated primarily at the translational level an d by limited proteolysis of polyproteins. Other virus groups also generate subgenomic mRNAs later in the reproductive cycle. For nidoviruses, subgenom ic mRNA synthesis (transcription) is discontinuous and yields a 5' and 3' c oterminal nested set of mRNAs, Nidovirus transcription is not essential for genome replication, which relies on the autoprocessing products of two rep licase polyproteins that are translated from the genome. We now show that t he N-terminal replicase subunit, nonstructural protein 1 (nsp1), of the nid ovirus equine arteritis virus is in fact dispensable for replication but cr ucial for transcription, thereby coupling replicase expression and subgenom ic mRNA synthesis in an unprecedented manner. Nsp1 is composed of two papai n-like protease domains and a predicted N-terminal zinc finger, which was i mplicated in transcription by site-directed mutagenesis, The structural int egrity of nsp1 is essential, suggesting that the protease domains form a pl atform for the zinc finger to operate in transcription.