Pleiotropic regulator 1 (PLRG1)

Pleiotropic regulator 1 (PLRG1) is a highly conserved core component of the spliceosome, essential for pre-mRNA splicing and alternative splice site selection. Structurally, it includes a WD repeat domain that facilitates protein-protein interactions within the spliceosomal CDC5L complex. Beyond its fundamental role in RNA processing, PLRG1 modulates cell cycle progression, ensures genome stability, and participates in DNA repair pathways. Pathologically, its expression is often upregulated in cancer, where it drives proliferation, enhances epithelial-to-mesenchymal transition, and promotes tumor progression. Experimental knockdown of PLRG1 in cancer cells induces mitotic arrest, microtubule destabilization, autophagy, ER stress, and apoptosis—with a more pronounced effect in malignant cells than in normal counterparts. These qualities make PLRG1 a novel candidate for anti-cancer therapeutic targeting, with its inhibition triggering tumor-specific cell death while offering mechanistic insight into core cellular processes.

Other names

PRL1PRP46PRPF46TANGO4Cwc1CDC5L complex subunitPleiotropic regulator 1Transport and Golgi organization 4 homologPleiotropic regulator 1 (PRL1 homolog, Arabidopsis)

RNA interference/shRNA/siRNA knockdown of PLRG1 leads to tumor cell death by causing mitotic defects, microtubule instability, cell cycle arrest, and DNA damage. Peptide inhibitors that disrupt CDC5L–PLRG1 interaction abolish spliceosome activity and thus impact cell viability.