Disruption of ZC3H15 Compromises Telomere Length Maintenance by Sequestering Telomerase within Cajal bodies

ABSTRACT: Telomere homeostasis, crucial for various biological processes, relies on telomerase activity. We identified ZC3H15 as a novel telomerase-interacting protein. Its deletion unexpectedly increased telomerase activity but led to shortened telomeres and cellular senescence. ZC3H15 interacts with telomerase and itself, regulating telomerase activity in an RNA-dependent manner. Proximity labeling showed ZC3H15's interaction with proteins involved in organelle assembly and RNA processes. Loss of ZC3H15 sequestered TERC in the Cajal body, reducing telomerase recruitment to telomeres during S phase. These findings unveil ZC3H15's role in telomere dynamics and cellular senescence, suggesting its potential as a target for cancer therapy or anti-aging interventions.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yan Huang  

PROVIDER: PXD052036 | iProX | Mon May 06 00:00:00 BST 2024

REPOSITORIES: iProX