Killing two birds with one stone: How the respiratory syncytial virus polymerase initiates transcription and replication

[...]M2-1 is only required for transcription elongation and does not affect initiation [23], and in vitro studies showed that L-P complexes were capable of initiating at either 1U or 3C in the absence of M2-1 or N [20, 24, 25]. [...]the L-P complex alone can initiate transcription or replication and...

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Bibliographic Details
Published in:PLoS pathogens 2019-02, Vol.15 (2), p.e1007548-e1007548
Main Authors: Noton, Sarah L, Tremaglio, Chadene Z, Fearns, Rachel
Format: Article
Language:English
Subjects:
Addition polymerization
Adenosine triphosphate
ATP
Binding sites
Biology and life sciences
DNA Replication - physiology
Elongation
Gene sequencing
Genes
Genomes
Genomics
GTP
Guanosine triphosphate
Humans
Low concentrations
Lung diseases
Medicine and Health Sciences
Messenger RNA
Mutation
Nucleotides
Pearls
Pediatric diseases
Proteins
Replicase
Replication
Replication initiation
Research and analysis methods
Respiratory syncytial virus
Respiratory Syncytial Virus Infections
Respiratory Syncytial Virus, Human - metabolism
Respiratory Syncytial Virus, Human - pathogenicity
Respiratory Syncytial Virus, Human - physiology
Respiratory Syncytial Viruses - metabolism
Respiratory Syncytial Viruses - pathogenicity
Respiratory Syncytial Viruses - physiology
Respiratory tract diseases
RNA
RNA polymerase
RNA Replicase - metabolism
RNA Replicase - physiology
Transcription (Genetics)
Transcription elongation
Transcription, Genetic - physiology
Virology
Virus Replication
Viruses
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Summary:[...]M2-1 is only required for transcription elongation and does not affect initiation [23], and in vitro studies showed that L-P complexes were capable of initiating at either 1U or 3C in the absence of M2-1 or N [20, 24, 25]. [...]the L-P complex alone can initiate transcription or replication and then mature into a fully competent transcriptase or replicase during elongation. Like other polymerases, the RSV polymerase requires a high concentration of initiating NTPs (ATP and GTP), but only initiation at 1U requires a very high concentration of NTP2 (CTP). Because CTP is only present at low concentrations in cells [29], this would present a barrier to replication initiation. [...]studies comparing promoter activities showed that the le has a much greater bias towards initiation from position 3 versus position 1 than the tr, and mutation analysis linked this to the nucleotides at positions 4 and 12 [6, 25]. [...]these small differences between the two promoters contribute to a hierarchy of RNA production of mRNA, genome, and antigenome (Fig 2). [...]an innate affinity for ATP and CTP would lend the polymerase additional stability during initiation opposite the 3ʹ terminal nucleotide, a challenging event for viruses with linear genomes. [...]the RSV promoter sequences have evolved so that different viral RNAs are produced in the appropriate amounts. [...]RSV provides an exquisite example of how a virus is able to accomplish multiple objectives with minimal genetic information.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1007548