117: Pol III–linked polyadenylation fuels SINE RNA accumulation during infection

️ Episode 117: Pol III–linked polyadenylation fuels SINE RNA accumulation during infection In this episode of PaperCast Base by Base, we explore how viral infection couples RNA polymerase III transcription with mRNA-like 3′ end processing to stabilize noncoding retrotransposon RNAs, revealing a conserved mechanism that boosts SINE RNA abundance during pathogenic stress. fileciteturn0file0 Study Highlights:Using murine gammaherpesvirus (MHV68) infection as a model, the authors show by Polr3A ChIP-seq that increased Pol III occupancy at type II promoters such as B2 SINEs and tRNA genes contributes to but does not fully explain SINE RNA accumulation. They develop a convolutional neural network (SAMBAR‑Net) that pinpoints a τ motif upstream of a polyadenylation signal as the key sequence feature of infection‑induced B2 SINE loci, with motif strength correlating with higher RNA levels. Infection recruits mRNA cleavage and polyadenylation machinery—including CPSF30 and CFIm25/Nudt21—to Pol III loci in a Brf1‑dependent manner, driving polyadenylation of B2 SINE RNAs that stabilizes these transcripts. Depletion of CPSF30 or Nudt21 diminishes B2 SINE polyadenylation and accumulation, and CPSF30 occupancy is also detected at human Alu elements and tRNA genes, indicating a conserved mechanism. Together, the findings uncover noncanonical, transcription‑associated polyadenylation as a regulator of Pol III RNAs during infection. Conclusion:Pol III–associated polyadenylation emerges as a central lever for stabilizing retrotransposon RNAs under stress, reframing virus–host control of noncoding RNA biogenesis and suggesting new molecular targets for intervention. Reference:Laria A, Shah SB, Mao X, Sanghrajka P, Karijolich J, Lareau LF, Glaunsinger BA. RNA polymerase III transcription–associated polyadenylation promotes the accumulation of noncoding retrotransposons during infection. Proceedings of the National Academy of Sciences. 2025;122(32):e2507186122. https://doi.org/10.1073/pnas.2507186122 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.castos.com/ Keywords: RNA polymerase III; SINE retrotransposons; polyadenylation; CPSF30/Nudt21; herpesvirus infection Chapters (00:00:00) - How viruses hijack our DNA(00:01:54) - How viral infections cause macular degeneration(00:07:09) - The polyadenylation of B2SIN NCRNAs(00:10:16) - Immunity and the polarity regulation of DNA(00:15:25) - Base by base