A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS

Murali Palangat1, Dan B Renner, David H Price

  • 1Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.

Insights

The principal negative elongation factor (NELF) and 5,6-dichloro-1-beta-D-ribobenzimidazole-sensitivity inducing factor (DSIF) inhibit RNA polymerase II transcription. This study reveals DSIF/NELF also inhibits transcript cleavage factor TFIIS, potentially regulating productive transcription.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Eukaryotic Transcription

Background:

  • RNA polymerase II promoter escape is crucial for gene regulation.
  • Negative elongation factors like DSIF/NELF and positive factors like P-TEFb control transcription.
  • DSIF/NELF inhibits early transcript elongation until P-TEFb intervenes.

Purpose of the Study:

  • To investigate previously undescribed activities of DSIF/NELF.
  • To understand the role of DSIF/NELF in regulating transcript elongation and processing.

Main Methods:

  • Investigated the interaction between DSIF/NELF and TFIIS.
  • Assessed the effect of DSIF/NELF on TFIIS activity at different transcript lengths.
  • Analyzed the mechanism of DSIF/NELF inhibition on nucleotide addition and TFIIS.

Main Results:

  • DSIF/NELF inhibits transcript cleavage factor TFIIS.
  • This TFIIS inhibition is mechanistically distinct from DSIF/NELF's inhibition of nucleotide addition.
  • TFIIS inhibition by DSIF/NELF occurs regardless of nascent RNA length.

Conclusions:

  • DSIF/NELF possesses a dual inhibitory mechanism: blocking elongation and inhibiting TFIIS.
  • TFIIS promotes promoter-proximal escape by cleaving back-tracked RNA.
  • DSIF/NELF's inhibition of TFIIS may serve as a negative regulatory mechanism for productive transcription.

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