Phase Separation Drives SARS-CoV-2 Replication : A Hypothesis
Vandelli, Andrea (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Vocino, Giovanni (University of Bologna)
Tartaglia, Gian Gaetano (Institució Catalana de Recerca i Estudis Avançats)

Data:	2022
Resum:	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.
Ajuts:	European Commission 309545 European Commission 855923 European Commission 727658 European Commission 825080 Agencia Estatal de Investigación PID 2020-117454RA-I00 Agencia Estatal de Investigación RYC 2019-026752-I
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Viral RNA ; Phase separation ; Stress granules ; Protein-rna interactions ; RNA-binding proteins
Publicat a:	Frontiers in Molecular Biosciences, Vol. 9 (May 2022) , art. 893067, ISSN 2296-889X

DOI: 10.3389/fmolb.2022.893067
PMID: 35647024

7 p, 1.0 MB

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