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The human U5 snRNP assembly factor, AAR2, regulates gene expression dependent on the PRPF8 protein

ABSTRACT: Small nuclear ribonucleoprotein complexes (snRNPs) represent the main subunits of the spliceosome. While the assembly of snRNP core particles has been well characterized, the incorporation of snRNP-specific proteins and the mechanisms of snRNP recycling after splicing are less well characterized. Furthermore, little is known about how targeted down-regulation of snRNP assembly factors impacts gene expression. U5 snRNP assembly in yeast requires the Aar2 protein, but the role of the human AAR2 homolog has not yet been investigated in detail. Here, we report a crystal structure of human AAR2 in complex with the RNase H-like domain of the U5-specific PRPF8 protein and in vitro interaction studies of AAR2 with U5 proteins, revealing similarities and differences in the interaction patterns compared to yeast Aar2p. Based on the structure, we probed the importance of interacting regions and residues, and designed AAR2 variants that failed to stably bind PRPF8 in vitro. SiRNA-mediated aar2 knock-down affected the expression levels of many genes. These effects were reversed by expressing siRNA-resistant PRPF8-binding AAR2 variants, but not by a phospho-mimetic AAR2 variant defective in PRPF8 binding. Our results reveal an unexpected role of an snRNP assembly factor in adjusting gene expression levels.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182977 | GEO | 2025/08/16

REPOSITORIES: GEO

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