8snx
Cryo-EM structure of the respiratory syncytial virus polymerase (L:P) bound to the leader promoter
Structural highlights
FunctionL_HRSVA Displays RNA-directed RNA polymerase, mRNA guanylyl transferase, mRNA (guanine-N(7)-)-methyltransferase and poly(A) synthetase activities. The viral mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). Functions either as transcriptase or as replicase. The transcriptase synthesizes subsequently the subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular protein N concentration. In this mode, the polymerase replicates the whole viral genome without recognizing the transcriptional signals (By similarity).[1] Publication Abstract from PubMedThe respiratory syncytial virus (RSV) polymerase is a multifunctional RNA-dependent RNA polymerase composed of the large (L) protein and the phosphoprotein (P). It transcribes the RNA genome into ten viral mRNAs and replicates full-length viral genomic and antigenomic RNAs(1). The RSV polymerase initiates RNA synthesis by binding to the conserved 3'-terminal RNA promoters of the genome or antigenome(2). However, the lack of a structure of the RSV polymerase bound to the RNA promoter has impeded the mechanistic understanding of RSV RNA synthesis. Here we report cryogenic electron microscopy structures of the RSV polymerase bound to its genomic and antigenomic viral RNA promoters, representing two of the first structures of an RNA-dependent RNA polymerase in complex with its RNA promoters in non-segmented negative-sense RNA viruses. The overall structures of the promoter-bound RSV polymerases are similar to that of the unbound (apo) polymerase. Our structures illustrate the interactions between the RSV polymerase and the RNA promoters and provide the structural basis for the initiation of RNA synthesis at positions 1 and 3 of the RSV promoters. These structures offer a deeper understanding of the pre-initiation state of the RSV polymerase and could aid in antiviral research against RSV. Structures of the promoter-bound respiratory syncytial virus polymerase.,Cao D, Gao Y, Chen Z, Gooneratne I, Roesler C, Mera C, D'Cunha P, Antonova A, Katta D, Romanelli S, Wang Q, Rice S, Lemons W, Ramanathan A, Liang B Nature. 2024 Jan;625(7995):611-617. doi: 10.1038/s41586-023-06867-y. Epub 2023 , Dec 20. PMID:38123676[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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