Patterns of RNA Editing in Newcastle Disease Virus Infections
The expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger...
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MDPI AG
2020-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/11/1249 |
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| author | Archana Jadhav Lele Zhao Alice Ledda Weiwei Liu Chan Ding Venugopal Nair Luca Ferretti |
| author_facet | Archana Jadhav Lele Zhao Alice Ledda Weiwei Liu Chan Ding Venugopal Nair Luca Ferretti |
| author_sort | Archana Jadhav |
| collection | DOAJ |
| description | The expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger number of guanines can be inserted with lower frequencies. We analysed data from deep RNA sequencing of samples from in vitro and in vivo NDV infections to uncover the patterns of mRNA editing in NDV. The distribution of insertions is well described by a simple Markov model of polymerase stuttering, providing strong quantitative confirmation of the molecular process hypothesised by Kolakofsky and collaborators three decades ago. Our results suggest that the probability that the NDV polymerase would stutter is about 0.45 initially, and 0.3 for further subsequent insertions. The latter probability is approximately independent of the number of previous insertions, the host cell, and viral strain. However, in LaSota infections, we also observe deviations from the predicted V/W ratio of about 3:1 according to this model, which could be attributed to deviations from this stuttering model or to further mechanisms downregulating the abundance of W protein. |
| first_indexed | 2024-03-10T15:08:42Z |
| format | Article |
| id | doaj.art-17abe5de0b64407e90085d4d9cf37c68 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:08:42Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-17abe5de0b64407e90085d4d9cf37c682023-11-20T19:31:35ZengMDPI AGViruses1999-49152020-11-011211124910.3390/v12111249Patterns of RNA Editing in Newcastle Disease Virus InfectionsArchana Jadhav0Lele Zhao1Alice Ledda2Weiwei Liu3Chan Ding4Venugopal Nair5Luca Ferretti6Viral Oncogenesis group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, UKBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UKMRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1NY, UKDepartment of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, ChinaDepartment of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai 200241, ChinaViral Oncogenesis group, The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, UKBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UKThe expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger number of guanines can be inserted with lower frequencies. We analysed data from deep RNA sequencing of samples from in vitro and in vivo NDV infections to uncover the patterns of mRNA editing in NDV. The distribution of insertions is well described by a simple Markov model of polymerase stuttering, providing strong quantitative confirmation of the molecular process hypothesised by Kolakofsky and collaborators three decades ago. Our results suggest that the probability that the NDV polymerase would stutter is about 0.45 initially, and 0.3 for further subsequent insertions. The latter probability is approximately independent of the number of previous insertions, the host cell, and viral strain. However, in LaSota infections, we also observe deviations from the predicted V/W ratio of about 3:1 according to this model, which could be attributed to deviations from this stuttering model or to further mechanisms downregulating the abundance of W protein.https://www.mdpi.com/1999-4915/12/11/1249polymerase stutteringpseudo-templated transcriptiondeep sequencing |
| spellingShingle | Archana Jadhav Lele Zhao Alice Ledda Weiwei Liu Chan Ding Venugopal Nair Luca Ferretti Patterns of RNA Editing in Newcastle Disease Virus Infections Viruses polymerase stuttering pseudo-templated transcription deep sequencing |
| title | Patterns of RNA Editing in Newcastle Disease Virus Infections |
| title_full | Patterns of RNA Editing in Newcastle Disease Virus Infections |
| title_fullStr | Patterns of RNA Editing in Newcastle Disease Virus Infections |
| title_full_unstemmed | Patterns of RNA Editing in Newcastle Disease Virus Infections |
| title_short | Patterns of RNA Editing in Newcastle Disease Virus Infections |
| title_sort | patterns of rna editing in newcastle disease virus infections |
| topic | polymerase stuttering pseudo-templated transcription deep sequencing |
| url | https://www.mdpi.com/1999-4915/12/11/1249 |
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