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Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene
Jordan Douglas1, Alexei J Drummond1, Richard L Kingston2
1Centre for Computational Evolution, University of Auckland, Auckland 1010, New Zealand.
Abstract:
The phosphoprotein gene of the paramyxoviruses encodes multiple protein products. The P, V, and W proteins are generated by transcriptional slippage. This process results in the insertion of non-templated guanosine nucleosides into the mRNA at a conserved edit site. The P protein is an essential component of the viral RNA polymerase and is encoded by a faithful copy of the gene in the majority of paramyxoviruses. However, in some cases, the non-essential V protein is encoded by default and guanosines must be inserted into the mRNA in order to encode P. The number of guanosines inserted into the P gene can be described by a probability distribution, which varies between viruses. In this article, we review the nature of these distributions, which can be inferred from mRNA sequencing data, and reconstruct the evolutionary history of cotranscriptional editing in the paramyxovirus family. Our model suggests that, throughout known history of the family, the system has switched from a P default to a V default mode four times; complete loss of the editing system has occurred twice, the canonical zinc finger domain of the V protein has been deleted or heavily mutated a further two times, and the W protein has independently evolved a novel function three times. Finally, we review the physical mechanisms of cotranscriptional editing via slippage of the viral RNA polymerase.
Insights
Paramyxoviruses generate multiple proteins from one gene through RNA editing. This process, involving guanosine insertions, shows varied evolutionary patterns and switches between P and V protein expression.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Paramyxoviruses utilize a single phosphoprotein gene to produce multiple proteins, including P, V, and W.
- These proteins arise from a process called transcriptional slippage, which inserts non-templated guanosine nucleosides into mRNA.
- This editing is crucial for generating the essential P protein, a component of the viral RNA polymerase.
Purpose of the Study:
- To review the nature of guanosine insertion probability distributions in paramyxoviruses.
- To reconstruct the evolutionary history of cotranscriptional editing within the paramyxovirus family.
- To examine the physical mechanisms underlying RNA editing via polymerase slippage.
Main Methods:
- Analysis of mRNA sequencing data to infer guanosine insertion probability distributions.
- Bioinformatic reconstruction of evolutionary events related to RNA editing.
- Review of existing literature on paramyxovirus RNA editing mechanisms.
Main Results:
- The system has switched between P and V default expression modes four times.
- Complete loss of the RNA editing system occurred twice.
- The V protein's zinc finger domain was deleted/mutated twice, and the W protein evolved new functions thrice.
Conclusions:
- Cotranscriptional editing in paramyxoviruses exhibits diverse evolutionary trajectories.
- The P and V protein expression balance is dynamically regulated through editing.
- Understanding these editing mechanisms provides insights into viral evolution and protein diversification.
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