The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain

Lidia Vasiljeva1, Minkyu Kim, Hannes Mutschler

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.

Insights

RNA polymerase II (Pol II) termination choice depends on protein recruitment. Nrd1 protein specifically binds to phosphorylated RNA polymerase II CTD, directing termination for short genes.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • RNA polymerase II (Pol II) mediates transcription termination through various mechanisms in Saccharomyces cerevisiae.
  • Specific protein factors dictate which termination pathway is utilized.
  • Nrd1, Nab3, and Sen1 form a complex involved in the termination of small nucleolar RNAs and other short transcripts.

Purpose of the Study:

  • To investigate the mechanism of pathway selection in RNA polymerase II transcription termination.
  • To understand the role of Nrd1 recruitment in determining termination specificity.
  • To elucidate the interaction between Nrd1 and the RNA polymerase II C-terminal domain (CTD).

Main Methods:

  • Analysis of Nrd1 recruitment to genes.
  • Biochemical assays to study protein-CTD interactions.
  • Structural analysis of the Nrd1 C-terminal domain (CID).

Main Results:

  • Nrd1 preferentially binds to the Ser5-phosphorylated form of the Pol II CTD.
  • This interaction explains Nrd1's association with gene 5' ends.
  • The Nrd1-Nab3-Sen1 pathway is specifically implicated in the termination of short Pol II-transcribed genes.

Conclusions:

  • Nrd1's CTD binding preference dictates its role in specific transcription termination pathways.
  • The recruitment of Nrd1 involves interactions with both the CTD and Nab3.
  • Understanding Nrd1's function provides insight into the regulation of transcription termination for distinct gene classes.

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