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Published on: December 23, 2020
How the Replication and Transcription Complex Functions in Jumping Transcription of SARS-CoV-2
Jianguang Liang1, Jinsong Shi2, Shunmei Chen3
1School of Pharmacy, Changzhou University, Changzhou, China.
Abstract:
Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC). Ascertaining all the RTC components and the arrangement of them is an indispensably step for the eventual determination of its global structure, leading to completely understanding all of its functions at the molecular level. Results: The main results include: 1) hairpins containing the canonical and non-canonical NSP15 cleavage motifs are canonical and non-canonical transcription regulatory sequence (TRS) hairpins; 2) TRS hairpins can be used to identify recombination regions in CoV genomes; 3) RNA methylation participates in the determination of the local RNA structures in CoVs by affecting the formation of base pairing; and 4) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Conclusions: In the present study, we proposed the theoretical arrangement of NSP12-15 and METTL3 in the global RTC structure and constructed a model to answer how the RTC functions in the jumping transcription of CoVs. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.
Insights
Scientists identified transcription regulatory sequence (TRS) hairpins, crucial for understanding coronavirus replication and transcription complex (RTC) function. These findings reveal RNA methylation
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, necessitates understanding its replication and transcription complex (RTC).
- Limited knowledge exists regarding the RTC's structure and function, hindering therapeutic development.
- Determining RTC components and their arrangement is vital for understanding its molecular functions.
Purpose of the Study:
- To elucidate the structure and function of the coronavirus replication and transcription complex (RTC).
- To investigate the role of transcription regulatory sequence (TRS) hairpins and RNA methylation in CoV gene expression.
- To propose a theoretical model for the RTC's global structure and function in jumping transcription.
Main Methods:
- Identification and analysis of canonical and non-canonical NSP15 cleavage motifs within TRS hairpins.
- Investigation of RNA methylation's impact on local RNA structures and base pairing in CoVs.
- Development of a theoretical model for the RTC, incorporating NSP12-15 and METTL3.
Main Results:
- Canonical and non-canonical TRS hairpins were identified, containing NSP15 cleavage motifs.
- TRS hairpins can serve as markers for identifying recombination regions within CoV genomes.
- RNA methylation influences local RNA structures by affecting base pairing, and METTL3 is crucial for RTC structure determination.
Conclusions:
- A theoretical model of the CoV RTC, including NSP12-15 and METTL3, was proposed to explain jumping transcription.
- TRS hairpins were newly reported to link NSP15 cleavage, RNA methylation, and CoV function at a molecular level.
- Findings enhance fundamental knowledge of gene expression and regulation in coronaviruses, providing a basis for future research.
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