Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Fission yeast (Schizosaccharomyces pombe) possesses 17 essential kinases for cell growth.
• These kinases regulate crucial processes like cell cycle progression, growth, polarity, and morphogenesis.
• Prp4 kinase is one such essential kinase involved in cellular functions.

Purpose of the Study:

• To investigate the role of Prp4 kinase in intron splicing.
• To characterize the specific conditions under which Prp4 kinase activity is required for splicing.

Main Methods:

• Characterization of Prp4 kinase activity on intron splicing using res1 and ppk8 genes.
• Extensive mutational analyses of splice sites and branch sequences.
• Assessment of interactions with U1 and U2 small nuclear RNAs (snRNAs).

Main Results:

• Splicing of the res1 intron, but not the ppk8 intron, was dependent on Prp4 kinase activity.
• Prp4 kinase dependence correlated with the strength of the 5' splice site and branch sequence.
• Proper transient interactions with U1 and U2 snRNAs were critical for Prp4-dependent splicing.

Conclusions:

• Prp4 kinase is required for the recognition and efficient splicing of introns with weak exon1/5' splice sites and weak branch sequences.
• The kinase plays a key role in ensuring accurate intron removal, especially under challenging sequence conditions.
• This highlights the intricate regulation of RNA splicing by essential kinases in eukaryotic cells.