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

Functional cluster

DNA-Directed RNA Polymerase Subunits

Experimental structures · PDB · 2

• 9IP2 EM 2.70A
• 9IP4 EM 2.84A

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0030430 host cell cytoplasm
• GO:0019013 viral nucleocapsid
• GO:0005524 ATP binding
• GO:0003924 GTPase activity
• GO:0046872 metal ion binding
• GO:0004482 mRNA 5'-cap (guanine-N7-)-methyltransferase 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 · 1

• GALIDESIVIR inhibitor

Related proteins · sequence + function similarity

• RNA-directed RNA polymerase L 1.00
• RNA-directed RNA polymerase L 1.00
• RNA-directed RNA polymerase L 1.00
• RNA-directed RNA polymerase L 1.00
• 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 0.92
• RNA-directed RNA polymerase L 0.92

Co-cited proteins · studied together in the literature

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

Literature · 3 cited papers

• Structural insights into the RNA-dependent RNA polymerase complexes from highly pathogenic Marburg and Ebola viruses. Nat. Commun. · 2025
• Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid protein VP30. J. Virol. · 2006
• The nucleotide sequence of the L gene of Marburg virus, a filovirus: homologies with paramyxoviruses and rhabdoviruses. Virology · 1992