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SPT6 functions in transcriptional pause/release via PAF1C recruitment

Yuki Aoi1, Avani P Shah1, Sheetal Ganesan1

  • 1Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Molecular Cell
|August 16, 2022
PubMed

Insights

SPT6 depletion releases paused RNA polymerase II (Pol II) by impairing PAF1C recruitment. This affects transcript maturity differently for short and long genes, revealing SPT6

Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • Biochemistry

Background:

  • Transcriptional elongation by RNA polymerase II (Pol II) is a complex process.
  • Factors regulating Pol II pause-release and productive elongation in vivo are not fully understood.

Purpose of the Study:

  • To investigate the role of SPT6 in regulating RNA Pol II transcriptional elongation.
  • To elucidate the cooperative mechanisms governing Pol II pause/release and productive elongation.

Main Methods:

  • Acute protein-depletion experiments.
  • Analysis of RNA Pol II behavior and transcript production.
  • Investigating protein-protein interactions and recruitment dynamics.

Main Results:

  • SPT6 depletion releases paused Pol II into gene bodies via impaired PAF1C recruitment.
  • Short genes show increased mature transcripts upon release; long genes fail to yield mature transcripts due to reduced processivity.
  • SPT6 depletion leads to NELF association with elongating Pol II without affecting elongation patterns.
  • SPT6 depletion impairs heat-shock-induced pausing.

Conclusions:

  • SPT6 plays a crucial role in regulating RNA Pol II pause/release and productive elongation.
  • SPT6 regulates these processes through PAF1C recruitment.
  • NELF does not appear to maintain the paused state of Pol II in this context.
Keywords:
NELFPAF1RNA polymerase IISPT6chromatinelongationgene expressionpause/releasepromoter-proximal pausingtranscription

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