An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA

Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit (TERT) contributes to cell physiology independently of its ability to elongate telomeres. Here we show that TERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease ( RMRP ), a gene that is mutated in the inherited pleiotropic syndrome cartilage–hair hypoplasia. Human TERT and RMRP form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer (also known as DICER1)-dependent manner. These observations identify a mammalian RdRP composed of TERT in complex with RMRP . TERT beyond the telomere Some types of RNA-mediated silencing involve the production of secondary siRNAs, made by converting single-stranded RNA into double-stranded RNA. This is done by the action of an RNA-dependent RNA polymerase (RdRP). Maida et al . now show that TERT, the catalytic subunit of telomerase, can generate dsRNA from the RNA component of mitochondrial RNA processing endoribonuclease ( RMRP ), previously shown to be mutated in cartilage–hair hypoplasia, an inherited form of dwarfism. The resulting dsRNA can be processed into siRNAs by the endoribonuclease Dicer. This is the first report of a mammalian RdRP activity. Evidence is accumulating to suggest that TERT contributes to cell physiology independently of its ability to elongate telomeres, and this new work points to one of the mechanisms involved. Accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit (TERT) has a role in cell physiology independent to that of elongating telomeres. Here it is shown to interact with RMRP , a gene that is mutated in the syndrome cartilage–hair hypoplasia, to form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNAs.