RNA-directed RNA polymerase L

Function

RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their capping and polyadenylation. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor. Capping is concomitant with initiation of mRNA transcription. Indeed, a GDP 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, both activities being carried by the viral polymerase. Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.

Classification

Family (Pfam)

PF14318 Mononeg_mRNAcap, PF00946 Mononeg_RNA_pol

InterPro

L_poly_C, Mononeg_mRNAcap, Mononeg_RNA_pol_cat, Mononega_L_MeTrfase, RNA-dir_pol_L_filovirus, SAM-dependent_MTases_sf

Functional cluster

DNA-Directed RNA Polymerase Subunits

Experimental structures · PDB · 1

• 9IP3 EM 3.10A

A predicted model is available from AlphaFold.

Gene Ontology · 10

• GO:0030430 host cell cytoplasm
• GO:0044423 virion component
• GO:0005524 ATP binding
• GO:0003924 GTPase activity
• GO:0046872 metal ion binding
• GO:0004482 mRNA 5'-cap (guanine-N7-)-methyltransferase activity
• GO:0097747 RNA polymerase activity
• GO:0003968 RNA-directed RNA polymerase activity
• GO:0039689 negative stranded viral RNA replication
• GO:0039697 negative stranded viral RNA transcription

Drugs targeting this protein · 2

• GALIDESIVIR inhibitor
• REMDESIVIR 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 0.99
• RNA-directed RNA polymerase L 0.98
• RNA-directed RNA polymerase L 0.98
• RNA-directed RNA polymerase L 0.97
• RNA-directed RNA polymerase L 0.97
• RNA-directed RNA polymerase L 0.97
• RNA-directed RNA polymerase L 0.97
• RNA-directed RNA polymerase L 0.95
• RNA-directed RNA polymerase L 0.94

Co-cited proteins · studied together in the literature

• RNA-directed RNA polymerase L 1 shared papers
• Polymerase cofactor VP35 3 shared papers
• Polymerase cofactor VP35 1 shared papers
• Membrane-associated protein VP24 2 shared papers
• Matrix protein VP40 2 shared papers
• Super small secreted glycoprotein 1 shared papers
• Transcriptional activator VP30 1 shared papers
• Nucleoprotein 1 shared papers
• Envelope glycoprotein 1 shared papers

Literature · 6 cited papers

• Structural insights into the RNA-dependent RNA polymerase complexes from highly pathogenic Marburg and Ebola viruses. Nat. Commun. · 2025
• Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus. Sci. Rep. · 2018
• Characterization of the catalytic center of the Ebola virus L polymerase. PLoS Negl. Trop. Dis. · 2017
• The L-VP35 and L-L interaction domains reside in the amino terminus of the Ebola virus L protein and are potential targets for antivirals. Virology · 2013
• Characterization of the L gene and 5' trailer region of Ebola virus. J. Gen. Virol. · 1999
• Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res. · 1993