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פותח על ידי קלירמאש פתרונות בע"מ -
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia
Year:
2014
Source of publication :
Nature Communications
Authors :
צינמון, יובל
;
.
Volume :
5
Co-Authors:
Boczonadi, V., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Müller, J.S., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Pyle, A., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Munkley, J., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Dor, T., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Quartararo, J., Department of Life Sciences, University of Parma, Parco Area delle Scienze 11A, Parma 43124, Italy
Ferrero, I., Department of Life Sciences, University of Parma, Parco Area delle Scienze 11A, Parma 43124, Italy
Karcagi, V., Department of Molecular Genetics and Diagnostics, NIEH, Albert Florian ut 2-6, Budapest 1097, Hungary
Giunta, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Polvikoski, T., Department of Pathology, Institute for Ageing and Health, Newcastle University, Campus for Ageing, Newcastle upon Tyne NE45PL, United Kingdom
Birchall, D., Neuroradiology Department, Regional Neurosciences Centre, Queen Victoria Road, Newcastle upon Tyne NE14PL, United Kingdom
Princzinger, A., Department of Paediatrics, Josa Andras Hospital, Szent Istvan utca 6, Nyiregyhaza 4400, Hungary
Cinnamon, Y., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel, Department of Poultry and Aquaculture Sciences, Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O.Box 6, Bet Dagan 50250, Israel
Lützkendorf, S., Department of Neuropediatrics, NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany
Piko, H., Department of Molecular Genetics and Diagnostics, NIEH, Albert Florian ut 2-6, Budapest 1097, Hungary
Reza, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Florez, L., Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 Perth, Australia
Santibanez-Koref, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Griffin, H., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Schuelke, M., Department of Neuropediatrics, NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany
Elpeleg, O., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Kalaydjieva, L., Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 Perth, Australia
Lochmüller, H., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Elliott, D.J., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Chinnery, P.F., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Edvardson, S., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Horvath, R., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Facilitators :
From page:
To page:
(
Total pages:
1
)
Abstract:
The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease. © 2014 Macmillan Publishers Limited.
Note:
Related Files :
Animals
Female
gene expression
gene silencing
Genetics
Male
molecular genetics
mutation
RNA
עוד תגיות
תוכן קשור
More details
DOI :
10.1038/ncomms5287
Article number:
4287
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
24144
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:05
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Scientific Publication
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia
5
Boczonadi, V., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Müller, J.S., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Pyle, A., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Munkley, J., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Dor, T., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Quartararo, J., Department of Life Sciences, University of Parma, Parco Area delle Scienze 11A, Parma 43124, Italy
Ferrero, I., Department of Life Sciences, University of Parma, Parco Area delle Scienze 11A, Parma 43124, Italy
Karcagi, V., Department of Molecular Genetics and Diagnostics, NIEH, Albert Florian ut 2-6, Budapest 1097, Hungary
Giunta, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Polvikoski, T., Department of Pathology, Institute for Ageing and Health, Newcastle University, Campus for Ageing, Newcastle upon Tyne NE45PL, United Kingdom
Birchall, D., Neuroradiology Department, Regional Neurosciences Centre, Queen Victoria Road, Newcastle upon Tyne NE14PL, United Kingdom
Princzinger, A., Department of Paediatrics, Josa Andras Hospital, Szent Istvan utca 6, Nyiregyhaza 4400, Hungary
Cinnamon, Y., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel, Department of Poultry and Aquaculture Sciences, Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O.Box 6, Bet Dagan 50250, Israel
Lützkendorf, S., Department of Neuropediatrics, NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany
Piko, H., Department of Molecular Genetics and Diagnostics, NIEH, Albert Florian ut 2-6, Budapest 1097, Hungary
Reza, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Florez, L., Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 Perth, Australia
Santibanez-Koref, M., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Griffin, H., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Schuelke, M., Department of Neuropediatrics, NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany
Elpeleg, O., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Kalaydjieva, L., Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 Perth, Australia
Lochmüller, H., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Elliott, D.J., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Chinnery, P.F., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
Edvardson, S., Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
Horvath, R., Institute of Genetic Medicine, Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Central Parkway, Newcastle upon Tyne NE13BZ, United Kingdom
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia
The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease. © 2014 Macmillan Publishers Limited.
Scientific Publication
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