Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms

BioRxiv : the Preprint Server for Biology
Nicholas C HustonAnna Marie Pyle

Abstract

SARS-CoV-2 is the positive-sense RNA virus that causes COVID-19, a disease that has triggered a major human health and economic crisis. The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form stable RNA structures and yet, as much as 97% of its 30 kilobases have not been structurally explored in the context of a viral infection. Our limited knowledge of SARS-CoV-2 genomic architecture is a fundamental limitation to both our mechanistic understanding of coronavirus life cycle and the development of COVID-19 RNA-based therapeutics. Here, we apply a novel long amplicon strategy to determine for the first time the secondary structure of the SARS-CoV-2 RNA genome probed in infected cells. In addition to the conserved structural motifs at the viral termini, we report new structural features like a conformationally flexible programmed ribosomal frameshifting pseudoknot, and a host of novel RNA structures, each of which highlights the importance of studying viral structures in their native genomic context. Our in-depth structural analysis reveals extensive networks of well-folded RNA structures throughout Orf1ab and reveals new aspects of SARS-CoV-2 genome architecture that distinguish it from other single-str...Continue Reading

Citations

Sep 11, 2020·Nature Structural & Molecular Biology·Katharina SchubertNenad Ban
Oct 18, 2020·Nucleic Acids Research·Pan LiQiangfeng Cliff Zhang
Dec 30, 2020·Viruses·Junxing ZhaoJingxin Wang
Feb 16, 2021·The Journal of General Virology·Asmita GuptaMurali Dharan Bashyam
Dec 29, 2020·Biochemical Society Transactions·Ilaria Manfredonia, Danny Incarnato
Feb 24, 2021·Nucleic Acids Research·Angelika AndrzejewskaKatarzyna Pachulska-Wieczorek

Datasets Mentioned

BETA
MN908947
MH002341
DQ415903
KU558923

Methods Mentioned

BETA
SHAPE-MaP
PCR
electrophoresis

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