The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
William C Hah - One of the best experts on this subject based on the ideXlab platform.
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an rna dependent rna polymerase formed by tert and the RMRP rna
Nature, 2009Co-Authors: Yoshiko Maida, Richard Possemato, Mami Yasukawa, Miho Furuuchi, Timo Lassma, Naoko Okamoto, Vivi Kasim, Yoshihide Hayashizaki, William C HahAbstract: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.
Jiaxiang Wang - One of the best experts on this subject based on the ideXlab platform.
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lncrna RMRP silence curbs neonatal neuroblastoma progression by regulating microrna 206 tachykinin 1 receptor axis via inactivating extracellular signal regulated kinases
Cancer Biology & Therapy, 2019Co-Authors: Juntao Pan, Da Zhang, Jiao Zhang, Pan Qin, Jiaxiang WangAbstract:ABSTRACTBackground: Neuroblastoma is the commonest malignancy in neonates. Long non-coding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to be an oncogenic factor in some malignancies. However, its roles and molecular mechanisms in neuroblastoma progression are poor defined.Methods: The expression of RMRP, microRNA-206 (miR-206), and tachykinin-1 receptor (TACR1) mRNA was measured by RT-qPCR assay. Protein levels of TACR1, phosphorylated extracellular signal-regulated kinases (ERK) 1/2 (p-ERK1/2) and ERK1/2 were detected by western blot assay. Cell proliferation was assessed by CCK-8 and colony formation assays. Cell migratory and invasive capacities were determined using Transwell migration and invasion assays. The interaction between miR-206 and RMRP or TACR1 was verified by luciferase assay. The roles and molecular mechanisms of RMRP knockdown on the growth of neuroblastoma xenografts were examined in vivo.Results: RMRP was highly expressed in neur...
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lncrna RMRP silence curbs neonatal neuroblastoma progression by regulating microrna 206 tachykinin 1 receptor axis via inactivating extracellular signal regulated kinases
Cancer Biology & Therapy, 2019Co-Authors: Juntao Pan, Da Zhang, Jiao Zhang, Pan Qin, Jiaxiang WangAbstract:Background: Neuroblastoma is the commonest malignancy in neonates. Long non-coding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to be an onco...
Luigi D. Notarangelo - One of the best experts on this subject based on the ideXlab platform.
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small rnas derived from lncrna rnase mrp have gene silencing activity relevant to human cartilage hair hypoplasia
Human Molecular Genetics, 2014Co-Authors: Leslie E. Rogler, Brian Kosmyna, David Moskowitz, Remon Bebawee, Joseph Rahimzadeh, Katrina M. Kutchko, Alain Laederach, Luigi D. Notarangelo, Silvia GilianiAbstract:Post-transcriptional processing of some long non-coding RNAs (lncRNAs) reveals that they are a source of miRNAs. We show that the 268-nt non-coding RNA component of mitochondrial RNA processing endoribonuclease, (RNase MRP), is the source of at least two short (∼20 nt) RNAs designated RMRP-S1 and RMRP-S2, which function as miRNAs. Point mutations in RNase MRP cause human cartilage –h air hypoplasia (CHH), and several disease-causing mutations map to RMRP-S1 and -S2. SHAPE chemical probing identified two alternative secondary structures altered by disease mutations. RMRP-S1 and -S2 are significantly reduced in two fibroblast cell lines and a B-cell line derived from CHH patients. Tests of gene regulatory activity of RMRP-S1 and -S2 identified over 900 genes that were significantly regulated, of which over 75% were down-regulated, and 90% contained target sites with seed complements of RMRP-S1 and -S2 predominantly in their 3 ′ UTRs. Pathway analysis identified regulated genes that function in skeletal development, hair development and hematopoietic cell differentiation includingPTCH2 andSOX4 among others, linked to major CHH phenotypes. Also, genes associated with alternative RNA splicing, cell proliferation and differentiation were highly targeted. Therefore, alterations RMRP-S1 and -S2, caused by point mutations in RMRP, are strongly implicated in the molecular mechanism of CHH.
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variability of clinical and laboratory features among patients with ribonuclease mitochondrial rna processing endoribonuclease gene mutations
The Journal of Allergy and Clinical Immunology, 2008Co-Authors: Fotini D Kavadas, Luigi D. Notarangelo, Silvia Giliani, Evelina Mazzolari, Andrea Bates, Eleonora Pegoiani, Chaim M RoifmanAbstract:Background Cartilage hair hypoplasia is an autosomal recessive type of metaphyseal chondrodysplasia, caused by mutations in the ribonuclease mitochondrial RNA processing ( RMRP ) gene. Typical features of cartilage hair hypoplasia include short stature, a predisposition to malignancy, and a variable degree of impairment of cellular immunity. Objective We sought to describe the heterogeneity of clinical and immunologic phenotype in 12 consecutive patients with RMRP mutations who were referred to 2 different institutions for immunologic evaluation. Methods We have retrospectively analyzed the clinical and laboratory features in 12 patients with molecular defects in the RMRP gene. T-cell repertoire was investigated by quantitating Vβ families' expression and analyzing their diversity. T-cell receptor excision circle analysis was used to study thymic output. Results All 12 patients had significant immune abnormalities, leading to severe immune deficiency in 9. CD8 lymphocytopenia was identified as a novel phenotype associated with RMRP mutations. Significant, even intrafamilial, phenotypic heterogeneity was observed. In 3 cases, severe immunodeficiency was the only phenotypic manifestation associated with RMRP mutations, a novel finding. Mutations leading to significant immune defects were most often located in the promoter, and the first case of a compound heterozygote for 2 such mutations is reported. Conclusion This report broadens the spectrum of phenotypes associated with RMRP mutations and suggests that mutations in this gene should be considered when evaluating patients with combined immune deficiency, regardless of the presence of other manifestations.
Yoshiko Maida - One of the best experts on this subject based on the ideXlab platform.
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Off-Target Effect of Endogenous siRNA Derived from RMRP in Human Cells
International journal of molecular sciences, 2013Co-Authors: Yoshiko Maida, Yoshihide Hayashizaki, Satoru Kyo, Timo Lassmann, Kenkichi MasutomiAbstract:Endogenous siRNAs (endo-siRNAs) are key regulators of RNA silencing in plants and worms; however, the biogenesis and function of endogenous siRNAs in mammals remain largely unknown. We previously demonstrated that human telomerase reverse transcriptase produces a self-targeting endogenous siRNA from non-coding RMRP RNA via RNA-dependent RNA polymerase (RdRP) activity. Here, we investigated whether the endo-siRNA derived from RMRP targets other genes in addition to RMRP. Four algorithms for microRNA target prediction were used to identify possible targets of the endo-siRNA, and the phytanoyl-CoA hydroxylase-interacting protein-like gene (PHYHIPL) was identified as the most promising candidate. The 3' UTR of PHYHIPL was found to contain three possible target sites with perfect seed pairing; deletion of each of these sites resulted in recovery of upstream luciferase expression. In addition, sequence-specific inhibition of the RMRP-derived endo-siRNA increased expression of PHYHIPL mRNA. The results described here suggest that the endo-siRNA uses silencing mechanisms that are similar to those used by microRNAs for gene silencing. To our knowledge, this study is the first confirmation of the off-target effect of human endogenous siRNA produced by RdRP activity.
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an rna dependent rna polymerase formed by tert and the RMRP rna
Nature, 2009Co-Authors: Yoshiko Maida, Richard Possemato, Mami Yasukawa, Miho Furuuchi, Timo Lassma, Naoko Okamoto, Vivi Kasim, Yoshihide Hayashizaki, William C HahAbstract: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.
Juntao Pan - One of the best experts on this subject based on the ideXlab platform.
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lncrna RMRP silence curbs neonatal neuroblastoma progression by regulating microrna 206 tachykinin 1 receptor axis via inactivating extracellular signal regulated kinases
Cancer Biology & Therapy, 2019Co-Authors: Juntao Pan, Da Zhang, Jiao Zhang, Pan Qin, Jiaxiang WangAbstract:ABSTRACTBackground: Neuroblastoma is the commonest malignancy in neonates. Long non-coding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to be an oncogenic factor in some malignancies. However, its roles and molecular mechanisms in neuroblastoma progression are poor defined.Methods: The expression of RMRP, microRNA-206 (miR-206), and tachykinin-1 receptor (TACR1) mRNA was measured by RT-qPCR assay. Protein levels of TACR1, phosphorylated extracellular signal-regulated kinases (ERK) 1/2 (p-ERK1/2) and ERK1/2 were detected by western blot assay. Cell proliferation was assessed by CCK-8 and colony formation assays. Cell migratory and invasive capacities were determined using Transwell migration and invasion assays. The interaction between miR-206 and RMRP or TACR1 was verified by luciferase assay. The roles and molecular mechanisms of RMRP knockdown on the growth of neuroblastoma xenografts were examined in vivo.Results: RMRP was highly expressed in neur...
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lncrna RMRP silence curbs neonatal neuroblastoma progression by regulating microrna 206 tachykinin 1 receptor axis via inactivating extracellular signal regulated kinases
Cancer Biology & Therapy, 2019Co-Authors: Juntao Pan, Da Zhang, Jiao Zhang, Pan Qin, Jiaxiang WangAbstract:Background: Neuroblastoma is the commonest malignancy in neonates. Long non-coding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) has been reported to be an onco...
