DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Alternative messenger RNA (mRNA) splicing generates proteomic complexity from a limited gene set.
• Splicing is coupled to transcription and influenced by transcript elongation rate.
• The connection between transcribing RNA polymerase II (RNAPII) and messenger ribonucleoprotein (mRNP) particles remains unclear.

Purpose of the Study:

• To characterize the human interactome of chromatin-associated mRNP particles.
• To identify factors linking RNAPII, mRNP particles, and splicing regulation.
• To elucidate the role of these factors in integrating transcription and splicing.

Main Methods:

• Human interactome analysis of chromatin-associated mRNP particles.
• Identification and characterization of protein complexes interacting with RNAPII.
• RNA-interference (RNAi)-mediated depletion to assess functional impact.
• Analysis of transcript elongation rates and alternative splicing patterns.

Main Results:

• Identified the DBIRD complex, containing DBC1 and ZNF326 (ZIRD), as a novel RNAPII interactor.
• DBIRD binds directly to RNAPII and is localized to affected exons.
• DBIRD regulates alternative splicing of exons in (A+T)-rich DNA.
• DBIRD depletion causes region-specific decreases in transcript elongation.

Conclusions:

• The DBIRD complex acts at the interface of mRNP particles and RNAPII.
• DBIRD integrates transcript elongation with the regulation of alternative splicing.
• This mechanism contributes to mammalian proteomic complexity.