Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Nature Communications | ||||
Verlag: | Nature | ||||
Ort der Veröffentlichung: | BERLIN | ||||
Band: | 11 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 1 | ||||
Datum: | 2020 | ||||
Institutionen: | Biologie und Vorklinische Medizin > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; INTELLECTUAL DISABILITY; ARGONAUTE PROTEINS; STRUCTURAL BASIS; MICRORNAS; GENE; PHOSPHORYLATION; RECOGNITION; CLEAVAGE; | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 49512 |
Zusammenfassung
ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 ...
Zusammenfassung
ARGONAUTE-2 and associated miRNAs form the RNA-induced silencing complex (RISC), which targets mRNAs for translational silencing and degradation as part of the RNA interference pathway. Despite the essential nature of this process for cellular function, there is little information on the role of RISC components in human development and organ function. We identify 13 heterozygous mutations in AGO2 in 21 patients affected by disturbances in neurological development. Each of the identified single amino acid mutations result in impaired shRNA-mediated silencing. We observe either impaired RISC formation or increased binding of AGO2 to mRNA targets as mutation specific functional consequences. The latter is supported by decreased phosphorylation of a C-terminal serine cluster involved in mRNA target release, increased formation of dendritic P-bodies in neurons and global transcriptome alterations in patient-derived primary fibroblasts. Our data emphasize the importance of gene expression regulation through the dynamic AGO2-RNA association for human neuronal development. AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.
Metadaten zuletzt geändert: 11 Okt 2021 12:40