دورية أكاديمية
أعرض في EDS

Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.

التفاصيل البيبلوغرافية
العنوان: Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.
المؤلفون: Fernandez SG; https://ror.org/01an7q238 Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA., Ferguson L; https://ror.org/01an7q238 Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.; https://ror.org/01an7q238 Center for Computational Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, CA, USA., Ingolia NT; https://ror.org/01an7q238 Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA ingolia@berkeley.edu.; https://ror.org/01an7q238 Center for Computational Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, CA, USA.
المصدر: Life science alliance [Life Sci Alliance] 2024 May 21; Vol. 7 (7). 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 Isoforms*/metabolism , Protein Isoforms*/genetics , Ribosomes*/metabolism , CCAAT-Enhancer-Binding Protein-alpha*/metabolism , CCAAT-Enhancer-Binding Protein-alpha*/genetics , Protein Biosynthesis*, Humans ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Animals ; Peptide Chain Initiation, Translational ; Mice ; TOR Serine-Threonine Kinases/metabolism ; HEK293 Cells
مستخلص: Translation initiation at alternative start sites can dynamically control the synthesis of two or more functionally distinct protein isoforms from a single mRNA. Alternate isoforms of the developmental transcription factor CCAAT/enhancer-binding protein α (C/EBPα) produced from different start sites exert opposing effects during myeloid cell development. This choice between alternative start sites depends on sequence features of the CEBPA transcript, including a regulatory uORF, but the molecular basis is not fully understood. Here, we identify the factors that affect C/EBPα isoform choice using a sensitive and quantitative two-color fluorescent reporter coupled with CRISPRi screening. Our screen uncovered a role of the ribosome rescue factor PELOTA (PELO) in promoting the expression of the longer C/EBPα isoform by directly removing inhibitory unrecycled ribosomes and through indirect effects mediated by the mechanistic target of rapamycin kinase. Our work uncovers further links between ribosome recycling and translation reinitiation that regulate a key transcription factor, with implications for normal hematopoiesis and leukemogenesis.
(© 2024 Fernandez et al.)
التعليقات: Update of: bioRxiv. 2023 Jan 17:2023.01.16.524343. doi: 10.1101/2023.01.16.524343. (PMID: 36711859)
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معلومات مُعتمدة: DP2 CA195768 United States CA NCI NIH HHS; R01 GM130996 United States GM NIGMS NIH HHS; S10 OD018174 United States OD NIH HHS
المشرفين على المادة: 0 (Protein Isoforms)
0 (CCAAT-Enhancer-Binding Protein-alpha)
0 (RNA, Messenger)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20240528 Date Completed: 20240528 Latest Revision: 20240610
رمز التحديث: 20240610
مُعرف محوري في PubMed: PMC11109482
DOI: 10.26508/lsa.202302501
PMID: 38803235
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-1077
DOI:10.26508/lsa.202302501