Tollervey lab paper featured in Molecular Cell. Authors Image Transcription elongation is a stochastic process that can go backwards as well as forwards. Here the authors report that folding of the nascent transcript immediately behind the polymerase resists backtracking and promotes forward movement. This results in faster elongation relative to unstructured sequences and is potentially important for cotranscriptional processing. Turowski, T.W., Petfalski, E., Goddard, B.D., French, S.L., Helwak, A., and Tollervey, D. Summary of Paper by Lori Koch RNA polymerases transcribe the genetic information stored in DNA into RNAs that carry out diverse functions in the cell. The process of transcription includes the initial engagement of the RNA polymerase with the DNA, the production of an RNA transcript based on complementarity with the DNA sequence, and finally the termination of elongation and disengagement of the polymerase. How much the specific sequence of the DNA/RNA affects the process of elongation remains unclear. In their recent paper in Molecular Cell, scientists in the Tollervey lab investigated this by comprehensively mapping RNA polymerase interactions with nascent transcripts. RNA polymerase is most commonly found at positions where it is moving most slowly. Looking closer at these sites, they found a tendency toward a higher G+C content, which means the RNA would interact more tightly with the DNA. More significantly, less RNA polymerase was found at places where tight folding of the newly synthesised RNA would occur, meaning that the polymerase was moving faster over such sequences. Next, they performed elegant in vitro transcription assays which confirmed that RNA folding stops the polymerase from moving backwards and helps push it forward. Mathematical modelling allowed the contribution of different effects to be disentangled, and confirmed that RNA folding has a major effect on the speed for the polymerase. Finally, they showed that this can affect the outcome of RNA processing by pre-mRNA splicing. Together, their work presents a compelling model for the regulation of transcription by the sequence-specific structure of nascent RNA transcripts. Related links Journal Link Tollervey Lab Website DOI This article was published on 2024-06-17
