期刊
VIRUSES-BASEL
卷 12, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/v12111249
关键词
polymerase stuttering; pseudo-templated transcription; deep sequencing
类别
资金
- Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/I/00007032, BBS/E/I/00007039, BB/R007896/1]
- BBSRC Newton Fund [BBS/OS/NW/000007]
- UK-India Joint Centre on Animal Technology
- BBSRC [BBS/E/I/00007039, BB/R007896/1, BBS/E/I/00007032] Funding Source: UKRI
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.
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