Regulation of protein synthesis is fundamental for all aspects of eukaryotic biology by controlling development, homeostasis and stress responses. The 13-subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes initiation factor and ribosome interactions required for productive translation. However, current understanding of eIF3 function does not explain genetic evidence correlating eIF3 deregulation with tissue-specific cancers and developmental defects. Here we report the genome-wide discovery of human transcripts that interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of messenger RNAs involved in cell growth control processes, including cell cycling, differentiation and apoptosis, via the mRNA 5' untranslated region. Surprisingly, functional analysis of the interaction between eIF3 and two mRNAs encoding the cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different modes of RNA stem-loop binding to exert either translational activation or repression. Our findings illuminate a new role for eIF3 in governing a specialized repertoire of gene expression and suggest that binding of eIF3 to specific mRNAs could be targeted to control carcinogenesis.
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http://dx.doi.org/10.1038/nature14267 | DOI Listing |
Cureus
November 2024
Laboratory of Genomic Medicine, GHC Genetics SK Ltd. Science Park, Comenius University in Bratislava, Bratislava, SVK.
In this article, we present a case study of a five-year-old girl with autism and developmental delay, conducted at the Academic Center for Autism Research in Bratislava, Slovakia. The girl was diagnosed using Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) instruments and met the criteria for autism spectrum disorder. Intellectual functioning was in the markedly below-average range, as indicated by the Snijders-Oomen Nonverbal Intelligence Test-Revised (SON-R) examination, and her level of adaptive functioning was significantly reduced.
View Article and Find Full Text PDFMol Cell
December 2024
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea. Electronic address:
Protein synthesis in the eukaryotic cytosol can start using both conventional methionine and formyl-methionine (fMet). However, a mechanism, if such exists, for detecting and regulating the incorporation of fMet (instead of Met) during translation, thereby preventing cellular toxicity of nascent fMet-bearing (fMet-) polypeptides, remains unknown. Here, we describe the fMet-mediated ribosome quality control (fMet-RQC) pathway in Saccharomyces cerevisiae.
View Article and Find Full Text PDFAnimals (Basel)
November 2024
Health and Environmental Research Center, Faculty of Environmental Management, Prince of Songkla University, Hat Yai 90110, Thailand.
infection, which causes visceral white spot disease, is a significant and economically devastating disease in aquaculture. In this study, we investigated the impact of bacterial infection on the protein composition of exosomes derived from the surface mucus of the hybrid grouper ♀ × ♂. Two hundred healthy fish were randomly separated into challenge and control groups.
View Article and Find Full Text PDFInt J Biol Sci
December 2024
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, P.R. China.
Over the past several decades, a canonical pathway called the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) mediating type I interferon (IFN) release via TANK-binding kinase 1(TBK1) / IFN regulatory factor 3 (IRF3) pathway has been widely investigated and characterized. Unexpectedly, recent studies show that the cGAS-STING noncanonically activates the protein kinase RNA-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α), an essential branch of unfolded protein response (UPR), even before the activation of the TBK1/IRF3 signaling. Additionally, we found that the PERK could regulate the STING signaling besides being modulated by upstream cGAS-STING.
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