Transcription of respiratory syncytial virus subgenomic positive sense mRNAs

Stable Identifier
R-HSA-9828639
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
cytosol
ReviewStatus
5/5
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Transcription of respiratory syncytial virus subgenomic positive sense mRNAs
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The RNA-dependent RNA polymerase complex (RdRP) of the human respiratory syncytial virus (RSV) is composed of large polymerase subunit L, which harbors catalytic activity, phosphoprotein polymerase cofactor subunit P, and transcription processivity factor M2-1. RdRP transcribes the RSV's negative sense, single-stranded RNA (-ssRNA) genome into 10 positive sense messenger RNAs that encode 11 viral proteins. The 10 viral mRNAs are: 1C (NS1) mRNA, 1B (NS2) mRNA, N mRNA, P mRNA, M mRNA, SH mRNA, G mRNA, F mRNA, M2 mRNA, and L mRNA. UV-based mapping shows that the 10 RSV genes are transcribed as a single transcriptional unit, with transcription of an individual gene depending on the prior transcription of all preceding genes (Dickens et al. 1984). The genomic RNA contains the 3' leader region of 44 nucleotides and the 5' trailer region, which are important for transcription initiation and termination, respectively. In addition, each RSV gene is preceded by a conserved GS (gene-start) motif and followed by a conserved GE (gene-end) motif, which regulate initiation and termination of transcription, respectively, of individual genes (Kuo et al. 1996; Kuo et al. 1997). GS signals in conjunction with nucleotides 36-45 of the 3' leader region are sufficient to direct accurate initiation of mRNA synthesis, with spacing between transcription signals being important (McGivern et al. 2005). M2-1 acts as a transcription processivity factor and its function depends on the Cys3-His1 motif consisting of 3 conserved cysteine residues C7, C15, and C21 and one conserved histidine residue, H25 (Tang et al. 2001).

NS1 mRNA is transcribed from the NS1 gene at the very 3' end of the RSV genome (Dickens et al. 1984, Collins and Wertz 1985, Evans et al. 1996) while NS2 mRNA is transcribed from the NS2 gene, located 5' terminally to the NS1 gene (Dickens et al. 1984, Venkatesan et al. 1983, Collins and Wertz 1985, Evans et al. 1996). While individual NS1 and NS2 mRNAs are thought to predominate, a dicistronic mRNA, containing both the NS1 and NS2 mRNA sequences separated by an intergenic sequence, has been reported (Collins and Wertz 1985). N mRNA is transcribed from the N gene (Venkatesan et al. 1983, Dickens et al. 1984). P mRNA is transcribed from the P gene (Venkatesan et al. 1983, Dickens et al. 1984). M mRNA is transcribed from the M gene (Venkatesan et al. 1983, Satake and Venkatesan 1984, Dickens et al. 1984). SH mRNA is transcribed from the SH gene (Dickens et al. 1984). G mRNA is transcribed from the G gene (Dickens et al. 1984). F mRNA is transcribed from the F gene (Dickens et al. 1984, Elango et al. 1985). M2 mRNA is transcribed from the M2 gene (Collins et al. 1987, Kuo et al. 1996, Fearns and Collins 1999). Dicistronic mRNAs F-M2 and M2-L as well as polycistronic G-F-M2 mRNA can also be detected (Fearns and Collins 1999). L mRNA is transcribed from the L gene (Collins et al. 1987, Kuo et al. 1996, Fearns and Collins 1999). As the GS motif of the L gene lies upstream of the GE motif of the M2 gene, the latter occupying nucleotides 56-68 of the L gene (Collins et al. 1987, Kuo et al. 1996), only a smaller portion of L gene transcripts are full-length polyadenylated mRNAs. A larger portion are truncated polyadenylated transcripts (Collins et al. 1987). Full-length L mRNA is present at ~1/6 of the level of M2 mRNA throughout the course of infection (Fearns and Collins 1999). Dicistronic M2-L mRNA can also be detected (Fearns and Collins 1999).

Heat shock protein HSPA8 (HSC70) positively regulates transcription of viral mRNAs (Munday et al. 2015), consistent with previous reports that RSV transcription requires, in addition to the RdRP complex, the presence of host cell factors (Barik 1992).

M2-2 promotes the switch from transcription of viral genes to replication of the viral genome for virion assembly (Bermingham et and Collins 1999). M2-2-mediated inhibition of transcription may require phosphorylation of the P protein on particular sites (Asenjo and Villanueva 2016).
Literature References
PubMed ID Title Journal Year
9847343 Model for polymerase access to the overlapped L gene of respiratory syncytial virus

Fearns, R, Collins, PL

J Virol 1999
6572388 Construction and characterization of cDNA clones for four respiratory syncytial viral genes

Venkatesan, S, Elango, N, Chanock, RM

Proc Natl Acad Sci U S A 1983
2998021 Nucleotide sequences of the 1B and 1C nonstructural protein mRNAs of human respiratory syncytial virus

Collins, PL, Wertz, GW

Virology 1985
11689613 Requirement of cysteines and length of the human respiratory syncytial virus M2-1 protein for protein function and virus viability

Tang, RS, Nguyen, N, Cheng, X, Jin, H

J Virol 2001
9188557 Analysis of the gene start and gene end signals of human respiratory syncytial virus: quasi-templated initiation at position 1 of the encoded mRNA

Kuo, L, Fearns, R, Collins, PL

J Virol 1997
15681446 Identification of internal sequences in the 3' leader region of human respiratory syncytial virus that enhance transcription and confer replication processivity

McGivern, DR, Collins, PL, Fearns, R

J Virol 2005
10500164 The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription

Bermingham, A, Collins, PL

Proc Natl Acad Sci U S A 1999
8794332 Effects of mutations in the gene-start and gene-end sequence motifs on transcription of monocistronic and dicistronic minigenomes of respiratory syncytial virus

Kuo, L, Grosfeld, H, Cristina, J, Hill, MG, Collins, PL

J Virol 1996
2440043 Gene overlap and site-specific attenuation of transcription of the viral polymerase L gene of human respiratory syncytial virus

Collins, PL, Olmsted, RA, Spriggs, MK, Johnson, PR, Buckler-White, AJ

Proc Natl Acad Sci U S A 1987
6492254 Transcriptional mapping of human respiratory syncytial virus

Dickens, LE, Collins, PL, Wertz, GW

J Virol 1984
1404620 Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s)

Barik, S

J Virol 1992
2987829 Respiratory syncytial virus fusion glycoprotein: nucleotide sequence of mRNA, identification of cleavage activation site and amino acid sequence of N-terminus of F1 subunit

Elango, N, Satake, M, Coligan, JE, Norrby, E, Camargo, E, Venkatesan, S

Nucleic Acids Res 1985
8864205 Expression and characterisation of the NS1 and NS2 proteins of respiratory syncytial virus

Evans, JE, Cane, PA, Pringle, CR

Virus Res 1996
6699948 Nucleotide sequence of the gene encoding respiratory syncytial virus matrix protein

Satake, M, Venkatesan, S

J Virol 1984
Participants
Input
Output
Participates
as an event of
Catalyst Activity

RNA-directed RNA polymerase activity of RdRP:p-M2-1:hRSV A nucleocapsid [cytosol]

Physical Entity
RdRP:p-M2-1:hRSV A nucleocapsid [cytosol] (Human respiratory syncytial virus A)
Activity
RNA-directed RNA polymerase activity (GO:0003968)
This event is regulated
Negatively by
Regulator
M2-2 [cytosol] (Human respiratory syncytial virus A)
Positively by
Regulator
HSPA8 [cytosol] (Homo sapiens)
Active Unit
HSPA8 [cytosol]
Disease
Cross References
Mondo
Authored
Orlic-Milacic, M  (2023-02-16)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Orlic-Milacic, M  (2023-02-16)
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