دورية أكاديمية
أعرض في EDS

Regulation of microRNA expression by the adaptor protein GRB2.

التفاصيل البيبلوغرافية
العنوان: Regulation of microRNA expression by the adaptor protein GRB2.
المؤلفون: Stainthorp AK; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Lin CC; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Wang D; LeedsOmics, University of Leeds, Leeds, LS2 9JT, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., Medhi R; Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK., Ahmed Z; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Suen KM; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Miska EA; Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK., Whitehouse A; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Ladbury JE; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. j.e.ladbury@leeds.ac.uk.
المصدر: Scientific reports [Sci Rep] 2023 Jun 16; Vol. 13 (1), pp. 9784. Date of Electronic Publication: 2023 Jun 16.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: MicroRNAs*/metabolism, Gene Silencing ; Base Sequence ; GRB2 Adaptor Protein/genetics ; GRB2 Adaptor Protein/metabolism ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism
مستخلص: Protein interactions with the microRNA (miRNA)-mediated gene silencing protein Argonaute 2 (AGO2) control miRNA expression. miRNA biogenesis starts with the production of precursor transcripts and culminates with the loading of mature miRNA onto AGO2 by DICER1. Here we reveal an additional component to the regulatory mechanism for miRNA biogenesis involving the adaptor protein, growth factor receptor-bound protein 2 (GRB2). The N-terminal SH3 domain of GRB2 is recruited to the PAZ domain of AGO2 forming a ternary complex containing GRB2, AGO2 and DICER1. Using small-RNA sequencing we identified two groups of miRNAs which are regulated by the binding of GRB2. First, mature and precursor transcripts of mir-17~92 and mir-221 miRNAs are enhanced. Second, mature, but not precursor, let-7 family miRNAs are diminished suggesting that GRB2 directly affects loading of these miRNAs. Notably, the resulting loss of let-7 augments expression of oncogenic targets such as RAS. Thus, a new role for GRB2 is established with implications for cancer pathogenesis through regulation of miRNA biogenesis and oncogene expression.
(© 2023. The Author(s).)
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معلومات مُعتمدة: 22356 United Kingdom CRUK_ Cancer Research UK; C57233/A22356 United Kingdom CRUK_ Cancer Research UK
المشرفين على المادة: 0 (MicroRNAs)
0 (GRB2 Adaptor Protein)
0 (Argonaute Proteins)
تواريخ الأحداث: Date Created: 20230616 Date Completed: 20230619 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC10276003
DOI: 10.1038/s41598-023-36996-3
PMID: 37328606
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-023-36996-3