Characterizing nascent readthrough transcripts in human cells

More than 75% of protein-coding genes show readthrough transcription in 16 human cell lines under homeostatic conditions, revealing widespread failure to terminate at the TES.

• Why it matters: Termination by RNAPII shapes transcriptome and proteome identity, but how it is regulated remains incompletely understood, especially for nascent readthrough.
• What they did: Using nascent RNA Bru-seq across 16 ENCODE 4 cell lines, the authors quantified readthrough and tested global changes after oxidative stress, hyperosmotic treatment, or splicing inhibition.
• The result: Oxidative stress, hyperosmotic conditions, and splicing inhibitors increase readthrough globally, and auxin-inducible depletion of BRD4, MED14, or XRN2 increases readthrough while SUPT16H depletion shortens it.

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