PubMed:31695036 JSON TXT

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PubMed_ArguminSci

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":127,"end":205},"obj":"DRI_Background"},{"id":"T2","span":{"begin":206,"end":293},"obj":"DRI_Approach"},{"id":"T3","span":{"begin":294,"end":388},"obj":"DRI_Background"},{"id":"T4","span":{"begin":389,"end":504},"obj":"DRI_Approach"},{"id":"T5","span":{"begin":505,"end":701},"obj":"DRI_Challenge"},{"id":"T6","span":{"begin":722,"end":723},"obj":"DRI_Challenge"},{"id":"T7","span":{"begin":724,"end":895},"obj":"DRI_Outcome"},{"id":"T8","span":{"begin":896,"end":1078},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1079,"end":1229},"obj":"DRI_Approach"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

Goldhamster2_Cellosaurus

{"project":"Goldhamster2_Cellosaurus","denotations":[{"id":"T1","span":{"begin":33,"end":34},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T2","span":{"begin":156,"end":159},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T3","span":{"begin":164,"end":165},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T4","span":{"begin":289,"end":292},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T5","span":{"begin":394,"end":396},"obj":"CVCL_5M23|Cancer_cell_line|Mesocricetus auratus"},{"id":"T6","span":{"begin":407,"end":408},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T7","span":{"begin":478,"end":479},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T8","span":{"begin":500,"end":503},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T9","span":{"begin":505,"end":508},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T10","span":{"begin":565,"end":572},"obj":"CVCL_0238|Cancer_cell_line|Homo sapiens"},{"id":"T11","span":{"begin":748,"end":750},"obj":"CVCL_5M23|Cancer_cell_line|Mesocricetus auratus"},{"id":"T12","span":{"begin":758,"end":759},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T13","span":{"begin":869,"end":870},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T14","span":{"begin":871,"end":874},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T15","span":{"begin":1050,"end":1053},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"},{"id":"T16","span":{"begin":1129,"end":1132},"obj":"CVCL_E773|Transformed_cell_line|Homo sapiens"},{"id":"T17","span":{"begin":1198,"end":1199},"obj":"CVCL_6479|Finite_cell_line|Mus musculus"},{"id":"T18","span":{"begin":1225,"end":1228},"obj":"CVCL_YL11|Embryonic_stem_cell|Homo sapiens"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

GoldHamster

Anatomy-MAT

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":109,"end":114},"obj":"Body_part"},{"id":"T2","span":{"begin":141,"end":146},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000041"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000041"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

HP-phenotype

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":115,"end":125},"obj":"Phenotype"},{"id":"T2","span":{"begin":183,"end":204},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0009830"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0009830"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

mondo_disease

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":115,"end":125},"obj":"Disease"},{"id":"T2","span":{"begin":127,"end":154},"obj":"Disease"},{"id":"T3","span":{"begin":156,"end":159},"obj":"Disease"},{"id":"T4","span":{"begin":183,"end":204},"obj":"Disease"},{"id":"T6","span":{"begin":289,"end":292},"obj":"Disease"},{"id":"T7","span":{"begin":500,"end":503},"obj":"Disease"},{"id":"T8","span":{"begin":505,"end":508},"obj":"Disease"},{"id":"T9","span":{"begin":871,"end":874},"obj":"Disease"},{"id":"T10","span":{"begin":1050,"end":1053},"obj":"Disease"},{"id":"T11","span":{"begin":1225,"end":1228},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005244"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0003620"},{"id":"A5","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005244"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/MONDO_0015626"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

NCBITAXON

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":480,"end":490},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":1061,"end":1071},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"2081351"},{"id":"A2","pred":"db_id","subj":"T1","obj":"32281"},{"id":"A3","pred":"db_id","subj":"T1","obj":"7215"},{"id":"A4","pred":"db_id","subj":"T4","obj":"2081351"},{"id":"A5","pred":"db_id","subj":"T4","obj":"32281"},{"id":"A6","pred":"db_id","subj":"T4","obj":"7215"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

Anatomy-UBERON

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":35,"end":42},"obj":"Body_part"},{"id":"T3","span":{"begin":109,"end":114},"obj":"Body_part"},{"id":"T4","span":{"begin":141,"end":146},"obj":"Body_part"},{"id":"T5","span":{"begin":339,"end":350},"obj":"Body_part"},{"id":"T6","span":{"begin":380,"end":387},"obj":"Body_part"},{"id":"T8","span":{"begin":661,"end":668},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005634"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000125"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0001091"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0001091"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/GO_0005634"},{"id":"A7","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0000125"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/GO_0005634"},{"id":"A9","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000125"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}

CL-cell

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":730,"end":738},"obj":"Cell"},{"id":"T2","span":{"begin":1177,"end":1184},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000540"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000540"}],"text":"Transcriptional dysregulation by a nucleus-localized aminoacyl-tRNA synthetase associated with Charcot-Marie-Tooth neuropathy.\nCharcot-Marie-Tooth disease (CMT) is a length-dependent peripheral neuropathy. The aminoacyl-tRNA synthetases constitute the largest protein family implicated in CMT. Aminoacyl-tRNA synthetases are predominantly cytoplasmic, but are also present in the nucleus. Here we show that a nuclear function of tyrosyl-tRNA synthetase (TyrRS) is implicated in a Drosophila model of CMT. CMT-causing mutations in TyrRS induce unique conformational changes, which confer capacity for aberrant interactions with transcriptional regulators in the nucleus, leading to transcription factor E2F1 hyperactivation. Using neuronal tissues, we reveal a broad transcriptional regulation network associated with wild-type TyrRS expression, which is disturbed when a CMT-mutant is expressed. Pharmacological inhibition of TyrRS nuclear entry with embelin reduces, whereas genetic nuclear exclusion of mutant TyrRS prevents hallmark phenotypes of CMT in the Drosophila model. These data highlight that this translation factor may contribute to transcriptional regulation in neurons, and suggest a therapeutic strategy for CMT."}