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RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression

Yoseop Yoon1, Elodie Bournique2, Lindsey V Soles1

  • 1Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.

Molecular Cell
|January 11, 2025
PubMed

Insights

Nuclear speckles (NSs) are key sites for pre-mRNA 3' processing in human cells. The protein RBBP6 links this essential mRNA biogenesis step to NSs, enhancing gene expression coordination.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Pre-messenger RNA (pre-mRNA) 3' processing is crucial for mRNA biogenesis.
  • The precise nuclear location of pre-mRNA 3' processing has remained elusive.

Purpose of the Study:

  • To identify the nuclear sites of pre-mRNA 3' processing.
  • To investigate the role of nuclear speckles (NSs) in this process.
  • To elucidate the function of retinoblastoma-binding protein 6 (RBBP6) in pre-mRNA 3' processing at NSs.

Main Methods:

  • Demonstration of RBBP6 association with NSs via its intrinsically disordered region (IDR).
  • In vitro pre-mRNA 3' processing assays using RBBP6 N-terminal domain (NTD).
  • Proximity labeling analyses to map pre-mRNA 3' processing sites relative to NSs.

Main Results:

  • Nuclear speckles (NSs) are identified as major sites for pre-mRNA 3' processing in human cells.
  • RBBP6 strongly associates with NSs through its C-terminal IDR, which is essential for efficient cellular processing.
  • Pre-mRNA 3' processing for over 50% of genes occurs in proximity to NSs.

Conclusions:

  • Nuclear speckles act as hubs coordinating transcription, splicing, and 3' processing.
  • NS localization of RBBP6 is critical for efficient pre-mRNA 3' processing in vivo.
  • This spatial organization enhances the coordination and efficiency of gene expression.
Keywords:
biomolecular condensatecleavage and polyadenylationgene expressionintrinsically disordered regionmembraneless organellenuclear specklephase separationpre-mRNA 3′ end processingtranscription termination

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