Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2

Version 1 : Received: 26 June 2024 / Approved: 26 June 2024 / Online: 26 June 2024 (10:45:44 CEST)

A peer-reviewed article of this Preprint also exists.

Patarca, R.; Haseltine, W.A. Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2. Int. J. Mol. Sci. 2024, 25, 8012. Patarca, R.; Haseltine, W.A. Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2. Int. J. Mol. Sci. 2024, 25, 8012.

Abstract

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally de-fined coronaviral enhancers, we detected via in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian IBV to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The open state would permit the enhancer to pair with remote sequences in the viral genome and modulate the expression of crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation possibly driven by decreased expression of the ORF3a immune evasion protein. The annotated enhancer sequences could inform structural prediction tools and antiviral interventions if validated experimentally.

Keywords

Coronavirus; enhancer; long-range RNA-RNA interactions; IBV; SARS-CoV-2; viral attenuation; host immune evasion

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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