The transcriptional gradient in negative-strand RNA viruses suggests a common RNA transcription mechanism
by Connor R. King, Casey-Tyler Berezin, Brian Munsky, Jean Peccoud Nonsegmented negative-strand RNA viruses (NNSV) are a diverse class of medically relevant viruses which display a conserved attenuation gradient in the transcription of their genomes. This gradient has been traditionally explained by the Stop-Start model which attributes attenuation to polymerase behavior at gene junctions. In this article, we evaluate an alternative explanation where the gradient arises from polymerase dynamics during transcription. We introduce the RNA Polymerase Association Mechanism (RAM) model, a coarse-grained stochastic framework that describes transcription using two parameters related to polymerase processivity and the ability of the polymerase to backtrack. The RAM model accurately reproduces transcriptional gradients across diverse NNSVs as well as in gene-shuffled VSV variants. Additionally, the inferred polymerase processivity appears correlated to the length of the viral genomes suggesting a conserved constraint on transcription across these viruses. While the RAM model does not account for all known molecular features of NNSV transcription, it provides a parsimonious and predictive framework for relating genome architecture and transcription. These results support the view that, in tandem with the traditional junction-centric mechanisms governing transcription, nonspecific attenuation mechanisms contribute to the NNSV transcriptional gradient and warrant closer inspection in future studies which could lead to better rational genome design in viral studies and biomedical applications.