RNA-directed RNA polymerase L
Also known as: L
Function
Responsible for RNA synthesis (replicase and transcriptase), cap addition, and cap methylation. Also performs the polyadenylation of subgenomic mRNAs by a stuttering mechanism at a slipery stop site present at the end of viral genes. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N) (Probable). The viral polymerase binds to the genomic RNA at two different sites in the 3' leader promoter thereby initiating either genome replication or mRNA transcription. In the transcription mode, the polymerase performs the sequential transcription of all mRNAs using a termination-reinitiation mechanism responding to gene start and gene end signals. Some polymerase disengage from the template at each gene junction, resulting in a decreasing abundance of transcripts from the 3' to the 5' end of the genome (Probable). The first gene is the most transcribed, and the last the least transcribed (Probable). Needs as cofactors the phosphoprotein for processivity and the M2-1 anti-termination protein. Polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides. Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation. In the replication mode, the polymerase replicates the whole viral genome without recognizing the gene end transcriptional signals. The ability of the polymerase to override the gene end signals as it is producing the antigenome is probably due to replicative RNA becoming encapsidated with nucleoprotein as it is synthesized.
Classification
- Family (Pfam)
- PF14314 Methyltrans_Mon_2nd, PF14318 Mononeg_mRNAcap, PF00946 Mononeg_RNA_pol
- InterPro
- L_methyltransferase_rhabdo, L_poly_C, Mononeg_mRNAcap, Mononeg_RNA_pol_cat, Mononega_L_MeTrfase
- Functional cluster
- RNase H & Viral Replication Proteins
Experimental structures · PDB · 10
- 6PZK EM 3.20A
- 6UEN EM 3.67A
- 8FPI EM 2.39A
- 8FU3 EM 2.88A
- 8SNX EM 3.40A
- 8SNY EM 3.41A
- 9C7Y EM 3.24A
- 9ECV EM 2.79A
- 9ED2 EM 2.72A
- 9N36 EM 2.72A
A predicted model is available from AlphaFold.
Gene Ontology · 8
Drugs targeting this protein · 2
- LUMICITABINE inhibitor
- PC-786 inhibitor
Related proteins · sequence + function similarity
- RNA-directed RNA polymerase L 1.00
- RNA-directed RNA polymerase L 0.99
- RNA-directed RNA polymerase L 0.99
- RNA-directed RNA polymerase L 0.95
- RNA-directed RNA polymerase L 0.93
- RNA-directed RNA polymerase L 0.93
- RNA-directed RNA polymerase L 0.92
- RNA-directed RNA polymerase L 0.89
- RNA-directed RNA polymerase L 0.89
- RNA-directed RNA polymerase L 0.89
- RNA-directed RNA polymerase L 0.89
- RNA-directed RNA polymerase L 0.89
Co-cited proteins · studied together in the literature
- Phosphoprotein 7 shared papers
- RNA-directed RNA polymerase L 2 shared papers
- Nucleoprotein 5 shared papers
- Protein M2-1 4 shared papers
- Phosphoprotein 1 shared papers
- Protein M2-2 4 shared papers
- Fusion glycoprotein F0 4 shared papers
- Major surface glycoprotein G 3 shared papers
- Matrix protein 3 shared papers
- Non-structural protein 2 3 shared papers
- Non-structural protein 1 3 shared papers
- Small hydrophobic protein 2 shared papers
Literature · 25 cited papers
- Structures of the promoter-bound respiratory syncytial virus polymerase. Nature · 2024
- Structural and mechanistic insights into the inhibition of respiratory syncytial virus polymerase by a non-nucleoside inhibitor. Commun. Biol. · 2023
- Conserved allosteric inhibitory site on the respiratory syncytial virus and human metapneumovirus RNA-dependent RNA polymerases. Commun. Biol. · 2023
- The methyltransferase domain of the Respiratory Syncytial Virus L protein catalyzes cap N7 and 2'-O-methylation. PLoS Pathog. · 2021
- Cryo-EM structure of the respiratory syncytial virus RNA polymerase. Nat. Commun. · 2020
- Structure of the human metapneumovirus polymerase phosphoprotein complex. Nature · 2020
- Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell · 2019
- Mechanism for de novo initiation at two sites in the respiratory syncytial virus promoter. Nucleic Acids Res. · 2018
- Polymerases of paramyxoviruses and pneumoviruses. Virus Res. · 2017
- Fine mapping and characterization of the L-polymerase-binding domain of the respiratory syncytial virus phosphoprotein. J. Virol. · 2015
- Factors affecting de novo RNA synthesis and back-priming by the respiratory syncytial virus polymerase. Virology · 2014
- Intracellular localization of human respiratory syncytial virus L protein. Arch. Virol. · 2007
- … and 13 more in the literature graph