Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Endoribonucleases / genetics*
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Gene Expression Regulation
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HeLa Cells
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Humans
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Protein Binding
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RNA, Double-Stranded / biosynthesis
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism
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RNA, Long Noncoding
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RNA, Small Interfering / biosynthesis
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism*
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RNA-Dependent RNA Polymerase / chemistry*
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RNA-Dependent RNA Polymerase / metabolism*
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Ribonuclease III / deficiency
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Ribonuclease III / genetics
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Ribonuclease III / metabolism
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Telomerase / genetics
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Telomerase / metabolism*
Substances
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RMRP non-coding RNA, human
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RNA, Double-Stranded
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RNA, Long Noncoding
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RNA, Small Interfering
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RNA, Untranslated
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Ribonucleoproteins
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RNA-Dependent RNA Polymerase
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TERT protein, human
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Telomerase
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Endoribonucleases
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mitochondrial RNA-processing endoribonuclease
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Ribonuclease III