Phase Separation Drives SARS-CoV-2 Replication: A Hypothesis

Frontiers in Molecular Biosciences

Giovanni Vocino⁴  Gian Gaetano Tartaglia⁵  Andrea Vandelli⁶ 

[1] Center for Human Technologies, Istituto Italiano di Tecnologia, Genova, Italy;Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain;Department of Biology ‘Charles Darwin’, Sapienza University of Rome, Rome, Italy;Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy;Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain;Universitat Pompeu Fabra (UPF), Barcelona, Spain;

关键词: viral RNA;    phase separation;    stress granules;    protein-RNA interactions;    RNA-binding proteins;   

DOI  :  10.3389/fmolb.2022.893067

来源: DOAJ

【 摘 要 】

Identifying human proteins that interact with SARS-CoV-2 genome is important to understand its replication and to identify therapeutic strategies. Recent studies have unveiled protein interactions of SARS-COV-2 in different cell lines and through a number of high-throughput approaches. Here, we carried out a comparative analysis of four experimental and one computational studies to characterize the interactions of SARS-CoV-2 genomic RNA. Although hundreds of interactors have been identified, only twenty-one appear in all the experiments and show a strong propensity to bind. This set of interactors includes stress granule forming proteins, pre-mRNA regulators and elements involved in the replication process. Our calculations indicate that DDX3X and several editases bind the 5′ end of SARS-CoV-2, a regulatory region previously reported to attract a large number of proteins. The small overlap among experimental datasets suggests that SARS-CoV-2 genome establishes stable interactions only with few interactors, while many proteins bind less tightly. In analogy to what has been previously reported for Xist non-coding RNA, we propose a mechanism of phase separation through which SARS-CoV-2 progressively sequesters human proteins hijacking the host immune response.

【 授权许可】

Unknown