SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape

• DOI: 10.1016/j.molcel.2021.08.029
• Publication Date: 2021-09-16T14:34:24Z
• Authors: Shibin Hu; Linna Peng; Congling Xu; Zhenning Wang; Aixia Song; Fei Xavier Chen
• Keywords: RNA polymerase II; Transcription; Enhancer RNAs; Transcription factories; RNA polymerase I

Transcription progression is governed by multitasking regulators including SPT5, an evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer activation to termination. Here we utilize a rapid degradation system and reveal crucial functions of SPT5 maintaining cellular chromatin RNA polymerase II (Pol II) levels. Rapid depletion causes pronounced reduction paused Pol at promoters enhancers, distinct negative elongation (NELF) resulting short-distance redistribution. Most genes exhibit downregulation, but not upregulation, accompanied greatly impaired transcription activation, altered landscape severe processivity defects gene bodies. Phosphorylation linker serine 666 potentiates pause release antagonized Integrator-PP2A (INTAC) targeting II, while phosphorylation the C-terminal region links 3′ end Our findings position as essential positive regulator global transcription.