CCAR-1 works together with the U2AF large subunit UAF-1 to regulate alternative splicing

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Background:

• Cell Division Cycle and Apoptosis Regulator (CCAR) proteins are emerging regulators of gene expression.
• CCAR proteins influence alternative splicing and transcription, impacting key physiological functions.
• Mammalian CCAR2/DBC1 integrates splicing with transcription, while C. elegans CCAR-1 affects the unc-52 gene.

Purpose of the Study:

• To investigate the genome-wide role of CCAR-1 in alternative splicing in C. elegans.
• To identify novel CCAR-1-regulated alternative splicing targets.
• To elucidate the functional interactions of CCAR-1 with spliceosome components.

Main Methods:

• RNA sequencing to identify genome-wide alternative splicing targets.
• Mass spectrometry to determine protein-protein interactions.
• Gene knockdown experiments in C. elegans.

Main Results:

• CCAR-1 regulates global alternative splicing patterns in C. elegans.
• New alternative splicing targets of CCAR-1 were identified.
• CCAR-1 interacts with spliceosome factors UAF-1 and UAF-2.
• Knockdown of ccar-1 impacts alternative splicing, motility, and proteostasis in UAF-1 mutant worms.

Conclusions:

• CCAR-1 is a key regulator of global alternative splicing in C. elegans.
• CCAR-1 functions in conjunction with spliceosome factor UAF-1.
• These findings expand our understanding of CCAR family functions in gene regulation.