The early RNA decay factor ZC3H18 directs first intron splicing.
ZC3H18 promotes first intron splicing by interacting with splicing factors, revealing a new role beyond its known function in RNA decay.
- Why it matters: Understanding how pre-mRNA splicing is regulated is crucial for gene expression control, yet the mechanisms linking the cap-binding complex to splicing and decay remain unclear.
- What they did: The study used genome-wide analysis and protein interaction assays to show that ZC3H18 interacts with splicing factors PRPF40A, PRP4K, and FNBP4, and that disrupting the CBC-ARS2-ZC3H18 axis impairs first intron splicing.
- The result: Findings suggest splicing factors displace ZC3H18 from the NEXT complex, favoring productive splicing over RNA decay, and provide mechanistic insight into cap-stimulated intron removal.