Interpretation! Uncover the fine structure of the full-length RNA genome of SARS-CoV-2 in infected cells!

July 29, 2020 // The COVID-19 pandemic caused by the single-stranded RNA virus SARS-CoV-2 will infect humans across species, and has spread rapidly worldwide, with more than 10 million infections, COVID-----? Symptoms of 19 infected people can range from mild to severe, including fever, cough, sore throat and shortness of breath, and scientists are still working on antiviral drugs and therapeutic methods, but they lack a complete understanding of the structural and biological mechanisms of SARS-CoV-2In a recent study published on the preprinted website bioRxiv entitled "Structure of The Full SARS-Cov-2 RNA Genome in Infected Cells", scientists from the Whitehead Institute for Biomedical Research described the RNA fine structure of SARS-CoV-2, which plays a key regulatory role in the virus transcription process, and revealed significant differences in the structure of some of the major drug target sites within the virusEarly studies of coronaviruses show that several conservative regions play a key role in virus replication, such as 5'UTR, 3'UTR, and Code Shifting Elements (FSE), and the calculation of experimental data, including RNAse probes and nuclear magnetic resonance (NMR) spectroscopy techniques, can be used to derive the structure of the virus, in addition, the secondary structures in these subgenomic regions are also important for the replication and transcription function of the virusFor example, FSE is located near the ORF1a/ORF1b boundary, and its role is to move the ribosome reading box to a nucleotide position, which bypasses the end of the END of ORF1a and provides the opportunity to expose ORF1b-encoded proteins, such as viral RNA-dependent RNA polymerase (RdRP), for many viruses, the speed of the change in the number of codes is strictly regulated because the small number of code changes will be caused by the large amount of the dna changeFor this reason, FSE has become a major therapeutic target, and researchers are now investigating whether small-molecule drugs can alter the sliding rate of ribosomes to inhibit the translation of viral proteinsPhoto credit: Tammy CTLan, et albioRxiv (2020) doi: 10.1101/2020.06.29.178343SARS-CoV FSE and SARS-CoV-2 are almost identical, with only one core The difference in nucleotides, the NMR results show that it is a false junction structure carrying three stems, the presence of this false junction structure causes the function of the ribosome to pause, and then reverse strain a nucleotide to release this tension, so far, the researchers do not know the displacement rate in SARS-CoV-2For FSE, there is currently no effective RNA structural model, and researchers do not know of CoVs' other functionally important genomic components, including most transcription regulatory sequences (TRS), which are critical for subgenome RNA (sgRNAs) transcriptionEarly silicon computational models could be improved by using chemical probes used for genome-wide RNA analysis, and now researchers use probes dimethyl sulfate (DMS) to detect secondary structures across the RNA genome, and the researchers say the results reveal significant differences in predictions within silicon wafers, while also highlighting the physiological structure of known functional components; Mutation analysis in cells, and sequencing was used for mutation analysis, as DMS was quickly paired with the cytosine of unpaired adenine in the body, and the researchers found 5 stem ring structures (SLs) in 5'UTRs) and three stem ring structures near the start of ORF1a, all of which had different important functionsThe replication of the virus requires SL1, while the region's highly conservative SL2 is also required for replication, and SL3 contains the leader TRS required for discontinuous transcription, and SL4 is necessary for sgRNA synthesis to maintain an appropriate distance between upstream and downstream stem ringsThe researchers also found that FSE can form two different structures within the cell (i.estructures 1 and 2), but later they need to further study whether to improve the efficiency of the shift by stopping the ribosome at the slip location rather than away from its locationPrevious studies have shown that the formation of false nodes or stable stems upstream of the sliding sequence can improve the transfer rate, but at present the researchers do not know whether there is a special study to analyze the translation efficiency of ORF1ab in infected cells, the researchers said that N protein can participate in binding and de-woundING TRS so that it can function, if the stability of TRS is changed may reduce affinity with N protein, and thus change the expression of sgRNAs, which may become another therapeutic targetOverall, researchers have found several major RNA structures throughout the genome, along with a new FSE model, and later researchers will continue to delve into the mechanisms and extent to clarify the mechanisms and extent to regulate ORF1ab translation of the alternative structure of SARS-CoV-2 FSE, and whether FSE can fold into a false junction in the cell, and the results may help scientists develop more treatments for SARS-CoV-2 later in life or preventive measuresRelated: 1 Structure of the Full SARS-CoV-2 RNA Genome in infected cells 2Tammy CLan, Matthew FAllan, Lauren EMalsick, et alStructure of the FULL SARS-CoV-2 RNA Genome in the infected cells, bioRxiv (2020) doi: 10.1101/2020.