Homo sapiens Raw sequence reads. Homo sapiens

Telomere homeostasis is essential for various biological processes and depends on the activity of telomerase. We found that ZC3H15 is a novel telomerase interacting protein. Its absence unexpectedly increased telomerase activity, but led to telomere shortening and cell aging. ZC3H15 interacts with telomerase and itself to regulate telomerase activity in an RNA-dependent manner. Proximity markers revealed that ZC3H15 interacts with proteins associated with organelle assembly and RNA processes. Loss of ZC3H15 sequestered TERC in Cajal and reduced telomerase recruitment of S-phase telomeres. These findings shed light on the role of ZC3H15 in telomere dynamics and cellular aging, suggesting that it has the potential to be a target for cancer therapy or anti-aging interventions.