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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., Telomerase is a ribonucleoprotein complex that elongates telomeres. Although several proteins interact with telomerase (1-4), the minimal components of active telomerase include the catalytic telomerase reverse transcriptase (TERT) and a [...]

The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unrelated origin. Immunization of mice with TERT RNA-transfected dendritic cells (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and thymoma tumor cells and inhibited the growth of three unrelated tumors in mice of distinct genetic backgrounds. TERT RNA-transfected human DC stimulated TERT-specific CTL in vitro that lysed human tumor cells, including Epstein Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with renal cancer, the patient's tumor cells were efficiently lysed by the CTL. Immunization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to include TERT as well as additional tumor antigens., Author(s): Smita K. Nair [1]; Axel Heiser [2]; David Boczkowski [1]; Anish Majumdar [3]; Michio Naoe [2]; Jane S. Lebkowski [3]; Johannes Vieweg [2]; Eli Gilboa (corresponding author) [1] Cytotoxic [...]

Researchers have discovered that retrotransposons and the reverse transcriptases (RTs) they encode may be beneficial to their hosts. Studies on over-expressed HO endonuclease in Saccharomyces cerevisiae revealed that retrotransposons and RTs are able to heal such chromosomal breaks. Previous studies have shown that RTs are essential components in the replication machinery of retroviruses such as HIV.

Researchers from the Gabriel and Haber laboratories have discovered that retrotransposons and the reverse transcriptases (RTs) they encode may be beneficial to their hosts. Studies on over-expressed HO endonuclease in Saccharomyces cerevisiae revealed that retrotransposons and RTs are able to heal such chromosomal breaks. Previous studies have shown that RTs are essential components in the replication machinery of retroviruses such as HIV.

The reverse transcription indicator gene his3AI was mixed with hybrid Ty/HIV elements to prove that HIV-1 RT/RH can replace the reverse transcriptase/ribonuclease H (RT/RH) of the Ty1 retrotransposon in Saccharomyces cerevisiae. Hybrid Ty/HIV-1 elements or HARTs were observed to give the first accurate living cells analyses for RNA-dependent polymerase and RNase H interactions of HIV-1 RT/RH outside the virus. A basic genetic assay in S. cerevisiae was recommended to be feasible for testing drugs that prevent the RT/RH of HIV-1.