Genes involved in pre-mRNA 3'-end formation and transcription termination revealed by a lin-15 operon Muv suppressor

Mingxue Cui1, Mary Ann Allen, Alison Larsen

  • 1Department of Molecular, Cellular, and Developmental Biology, and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309.

Insights

Researchers identified key proteins involved in RNA polymerase II transcription termination. These include factors for mRNA 3'-end formation and release, connecting transcription to RNA cleavage and termination.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Transcription termination by RNA polymerase II (Pol II) is crucial for gene expression, involving mRNA 3'-end formation and Pol II release.
  • Specific protein complexes, including cleavage polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF), recognize 3' processing signals.

Purpose of the Study:

  • To identify novel proteins involved in transcription termination processes at gene 3' ends.
  • To elucidate the roles of these proteins in connecting mRNA processing with Pol II release.

Main Methods:

  • Utilized a genetic screen in Caenorhabditis elegans exploiting a gene transposition mutation.
  • Identified suppressor mutations restoring normal gene expression.
  • Characterized the function of identified suppressor genes and encoded proteins.

Main Results:

  • Confirmed the involvement of known factors CPSF and CstF in transcription termination.
  • Discovered three novel suppressors encoding proteins with a domain interacting with the C-terminal domain of Pol II (CID).
  • Demonstrated that two CID proteins are essential for efficient 3' cleavage, linking termination and RNA cleavage.
  • Implicated a serine/arginine-rich (SR) protein, SRp20, in events post-3'-end cleavage, facilitating transcription termination.

Conclusions:

  • Identified novel protein factors, including CID and SRp20, that regulate RNA polymerase II transcription termination.
  • Established a functional link between mRNA 3'-end processing and the release of Pol II from DNA.
  • Provided new insights into the molecular mechanisms governing transcription termination in eukaryotes.

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