Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing

Area of Science:

• Molecular Biology
• Gene Expression Regulation
• RNA Splicing

Background:

• Eukaryotic gene expression relies on RNA splicing to remove introns from pre-mRNAs.
• Spliceosomes must accurately process diverse introns for functional messenger RNA (mRNA) generation.

Purpose of the Study:

• To investigate the function of Sde2, a novel splicing regulator in *Schizosaccharomyces pombe* (fission yeast).
• To elucidate the mechanism of Sde2 activation and its role in intron-specific pre-mRNA splicing.

Main Methods:

• Characterization of Sde2 protein structure and processing.
• Analysis of Sde2's role in splicing using genetic interactions and pre-mRNA splicing assays.
• Investigating the interaction between Sde2 and Cactin/Cay1.

Main Results:

• Sde2 is a ubiquitin-fold-containing protein requiring processing by Ubp5 and Ubp15 for activation.
• Activated Sde2-C, a short-lived fragment, is incorporated into spliceosomes.
• Loss or impaired activation of Sde2 leads to inefficient intron removal from specific pre-mRNAs.
• Sde2 facilitates the association of Cactin/Cay1 with spliceosomes.

Conclusions:

• Ubiquitin-like processing of Sde2 generates a transient, active form essential for splicing.
• Sde2 acts as an intron-specific splicing regulator, potentially serving as a checkpoint for proper gene expression.
• A functional link exists between Sde2 and Cactin/Cay1 in pre-mRNA splicing regulation.