Co-transcriptional RNA processing boosts zygotic genes and restrains noncoding transcription
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ABSTRACT: Transcription decodes protein-coding genes and interprets regulatory information embedded in the genome by generating RNA. In eukaryotes, gene transcription is coupled with RNA processing via the carboxyl terminal domain (CTD) of RNA polymerase (Pol) II to enhance mRNA production. Here we propose that co-transcriptional RNA processing is essential for zygotic gene activation (ZGA), which shifts from noncoding to protein-centered gene expression post-fertilization. Truncating the Pol II CTD in mouse embryonic stem cells disrupts this coupling, halting global mRNA synthesis and causing widespread intergenic transcription. This triggers transcriptional and epigenetic reprogramming and nuclear reorganization towards totipotency, resembling early two-cell embryos before ZGA. Mechanistically, the CTD suppresses noncoding transcription by restraining polymerase activity on chromatin, but facilitates promoter-proximal pausing, transcription directionality, velocity, and elongation efficacy at genes through coupled RNA processing. The evolution of longer CTD lengths enhances gene activity, likely accommodating the increasingly abundant noncoding genome sequences in mammals.
ORGANISM(S): Mus musculus
PROVIDER: GSE272962 | GEO | 2026/06/06
REPOSITORIES: GEO
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