دورية أكاديمية
IGHMBP2 deletion suppresses translation and activates the integrated stress response.
العنوان: | IGHMBP2 deletion suppresses translation and activates the integrated stress response. |
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المؤلفون: | Park J; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.; https://ror.org/043mz5j54 Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Desai H; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA., Liboy-Lugo JM; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.; https://ror.org/043mz5j54 Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Gu S; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA., Jowhar Z; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.; https://ror.org/043mz5j54 Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Xu A; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.; https://ror.org/043mz5j54 Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA., Floor SN; https://ror.org/043mz5j54 Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA stephen@floorlab.org.; https://ror.org/043mz5j54 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. |
المصدر: | Life science alliance [Life Sci Alliance] 2024 May 21; Vol. 7 (8). Date of Electronic Publication: 2024 May 21 (Print Publication: 2024). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]- |
مواضيع طبية MeSH: | Protein Biosynthesis*/genetics , Transcription Factors*/genetics , Transcription Factors*/metabolism , Stress, Physiological*/genetics , DNA-Binding Proteins*/genetics , DNA-Binding Proteins*/metabolism, Humans ; K562 Cells ; Activating Transcription Factor 4/genetics ; Activating Transcription Factor 4/metabolism ; Gene Deletion ; Gene Expression Regulation ; RNA, Transfer/genetics ; RNA, Transfer/metabolism |
مستخلص: | IGHMBP2 is a nonessential, superfamily 1 DNA/RNA helicase that is mutated in patients with rare neuromuscular diseases SMARD1 and CMT2S. IGHMBP2 is implicated in translational and transcriptional regulation via biochemical association with ribosomal proteins, pre-rRNA processing factors, and tRNA-related species. To uncover the cellular consequences of perturbing IGHMBP2 , we generated full and partial IGHMBP2 deletion K562 cell lines. Using polysome profiling and a nascent protein synthesis assay, we found that IGHMBP2 deletion modestly reduces global translation. We performed Ribo-seq and RNA-seq and identified diverse gene expression changes due to IGHMBP2 deletion, including ATF4 up-regulation. With recent studies showing the integrated stress response (ISR) can contribute to tRNA metabolism-linked neuropathies, we asked whether perturbing IGHMBP2 promotes ISR activation. We generated ATF4 reporter cell lines and found IGHMBP2 knockout cells demonstrate basal, chronic ISR activation. Our work expands upon the impact of IGHMBP2 in translation and elucidates molecular mechanisms that may link mutant IGHMBP2 to severe clinical phenotypes. (© 2024 Park et al.) |
التعليقات: | Update of: bioRxiv. 2023 Dec 12:2023.12.11.571166. doi: 10.1101/2023.12.11.571166. (PMID: 38168189) |
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معلومات مُعتمدة: | R35 GM149255 United States GM NIGMS NIH HHS; S10 OD028511 United States OD NIH HHS |
المشرفين على المادة: | 0 (Transcription Factors) 0 (IGHMBP2 protein, human) 0 (DNA-Binding Proteins) 145891-90-3 (Activating Transcription Factor 4) 0 (ATF4 protein, human) 9014-25-9 (RNA, Transfer) |
تواريخ الأحداث: | Date Created: 20240528 Date Completed: 20240528 Latest Revision: 20240610 |
رمز التحديث: | 20240610 |
مُعرف محوري في PubMed: | PMC11109757 |
DOI: | 10.26508/lsa.202302554 |
PMID: | 38803225 |
قاعدة البيانات: | MEDLINE |
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