2024/01/12 by Mukulika Ray, Julia Zaborowsky, Pranav Mahableshwarkar +15 · 1 voice
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer
paper · pdf · doi:10.1101/2024.01.11.575216
openalex publication_date 2024/01/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Summary How RNA splicing events are targeted to the correct genomic locations in specific cellular contexts to generate context-specific transcript diversity and prevent deleterious cryptic splicing remains very poorly understood. We show that a functionally conserved GA-rich DNA-binding transcription factor (TF), CLAMP, targets distinct RNA molecules in male and female cells to precisely regulate sex-specific splicing events through physical and functional interactions with RNA and RNA-binding proteins (RBPs). The prion-like domain of CLAMP (PrLD) and a stem-loop region in the target RNA are important for CLAMP-RNA interaction. Moreover, the CLAMP PrLD domain regulates sex-specific splicing by modulating the dynamics of an hnRNPA2/B1 family protein that regulates alternative splicing. Thus, we demonstrate that a TF targets co-transcriptional splicing to the correct genomic locations by directly linking DNA binding sites to RNA targets and modulating the dynamics of RBP partners that drive alternative splicing.