Eukaryotic gene expression requires the ordered association of numerous factors with precursor messenger RNAs (premRNAs)/messenger RNAs (mRNAs) to achieve efficiency and regulation. Here, we use the Balbiani ring (BR) genes to demonstrate the temporal and spatial association of the exon junction complex (EJC) core with gene-specific endogenous premRNAs and mRNAs. The EJC core components bind cotranscriptionally to BR premRNAs during or very rapidly after splicing. The EJC core does not recruit the nonsense-mediated decay mediaters UPF2 and UPF3 until the BR messenger RNA protein complexes (mRNPs) enter the interchromatin. Even though several known adapters for the export factor NXF1 become part of BR mRNPs already at the gene, NXF1 binds to BR mRNPs only in the interchromatin. In steady state, a subset of the BR mRNPs in the interchromatin binds NXF1, UPF2, and UPF3. This binding appears to occur stochastically, and the efficiency approximately equals synthesis and export of the BR mRNPs. Our data provide unique in vivo information on how export competent eukaryotic mRNPs are formed.
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http://dx.doi.org/10.1083/jcb.201412017 | DOI Listing |
AJNR Am J Neuroradiol
January 2025
School of Biomedical Engineering and Imaging Sciences (S.E.J.C.), King's College London, London, UK
Background: Intrameatal vascular loops (IVL) entering the internal auditory meatus and neurovascular contact (NVC) with the vestibulocochlear nerve (cranial nerve [CN] VIII) have been proposed to have a relationship with audiovestibular symptoms.
Purpose: This systematic review and meta-analysis aimed to determine whether the presence of IVLs and CN VIII NVC on MRI is associated with tinnitus, sensorineural hearing loss (SNHL), or vertigo and any specific subtypes.
Data Sources: All studies comparing the presence of IVL or CN VIII NVC in ears with these audiovestibular symptoms and controls were identified through MEDLINE, EMBASE, the Web of Science Core Collection, Scopus, and the Cochrane Register of Controlled Trials databases.
Cell Rep
September 2024
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Duke Institute for Brain Sciences and Duke Regeneration Center, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
The exon junction complex (EJC), nucleated by EIF4A3, is indispensable for mRNA fate and function throughout eukaryotes. We discover that EIF4A3 directly controls microtubules, independent of RNA, which is critical for neural wiring. While neuronal survival in the developing mouse cerebral cortex depends upon an intact EJC, axonal tract development requires only Eif4a3.
View Article and Find Full Text PDFMol Ther
August 2024
Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangdong 510080, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangdong 510080, China. Electronic address:
N6-methyladenosine (mA) is the most abundant endogenous modification in eukaryotic RNAs. It plays important roles in various biological processes and diseases, including cancers. More and more studies have revealed that the deposition of mA is specifically regulated in a context-dependent manner.
View Article and Find Full Text PDFCell Mol Life Sci
March 2024
PhyMedExp, Univ Montpellier, CNRS, INSERM, Montpellier, France.
Deposition of the exon junction complex (EJC) upstream of exon-exon junctions helps maintain transcriptome integrity by preventing spurious re-splicing events in already spliced mRNAs. Here we investigate the importance of EJC for the correct splicing of the 2.2-megabase-long human DMD pre-mRNA, which encodes dystrophin, an essential protein involved in cytoskeletal organization and cell signaling.
View Article and Find Full Text PDFJ Am Coll Cardiol
February 2024
Fred Hutchinson Cancer Center, Seattle, Washington, USA; Seattle Children's Hospital, Seattle, Washington, USA; University of Washington, Seattle, Washington, USA.
Background: Adult survivors of childhood cancer are at risk for cardiovascular events.
Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.
Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.
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