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bioRxiv · 10.64898/2026.01.11.698887

Evolutionary conservation and innovations of RNA polymerase II transcription elongation factors

Francette, A. M.·Grover, A.·Clark, N.·Arndt, K. M.
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Abstract

In eukaryotes, transcription elongation factors (TEFs) associate with RNA Polymerase II (RNAPII) to facilitate gene expression and couple transcription to co-transcriptional processes, including chromatin regulation and RNA processing. To further our understanding of TEF biology, we developed a domain-centric analysis pipeline to perform a broad survey of ten TEF orthologs -- Paf1, Ctr9, Cdc73, Rtf1, Leo1, Spt4, Spt5, Spt6, Spn1, and Elf1 -- across the Tree of Life and analyze their evolutionary patterns in a structural context. We report evidence for all ten TEFs being present in the last eukaryotic common ancestor, indicating that mechanisms of TEF-mediated transcription regulation are both ancient and conserved. However, some early-diverging eukaryotic clades exhibit signs of altered TEF domain composition. A comparative phylogenetic analysis highlighted conserved regions of TEFs that are detected in both metazoans and fungi and other regions that appear clade-specific, detected only in metazoans. These observations, together with additional insights generated from evolutionary rate covariation analysis, shed light on under-characterized aspects of TEFs, including domains for which functions have yet to be dissected.

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Francette, A. M., Grover, A., Clark, N., Arndt, K. M.. 2026-01-11. Evolutionary conservation and innovations of RNA polymerase II transcription elongation factors. https://doi.org/10.64898/2026.01.11.698887

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