Alternative splicing of pre-mRNAs can rapidly regulate the expression of large groups of proteins. The RNA binding protein TRA2B (SFRS10) plays well-established roles in developmentally regulated alternative splicing during Drosophila sexual differentiation. TRA2B is also essential for mammalian embryogenesis and is implicated in numerous human diseases. Precise regulation of alternative splicing is critical to the development and function of the central nervous system; however, the requirements for specific splicing factors in neurogenesis are poorly understood. This study focuses on the role of TRA2B in mammalian brain development. We show that, during murine cortical neurogenesis, TRA2B is expressed in both neural progenitors and cortical projection neurons. Using cortex-specific Tra2b mutant mice, we show that TRA2B depletion results in apoptosis of the neural progenitor cells as well as disorganization of the cortical plate. Thus, TRA2B is essential for proper development of the cerebral cortex.
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http://dx.doi.org/10.1002/cne.23405 | DOI Listing |
J Muscle Res Cell Motil
January 2025
Institute of Developmental and Regenerative Medicine, University of Oxford, IMS-Tetsuya Nakamura Building, Old Road Campus, Roosevelt Dr, Headington, Oxford, OX3 7TY, UK.
Recent years have seen enormous progress in the field of advanced therapeutics for the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). In particular, four antisense oligonucleotide (ASO) therapies targeting various DMD-causing mutations have achieved FDA approval, marking major milestones in the treatment of this disease. These compounds are designed to induce alternative splicing events that restore the translation reading frame of the dystrophin gene, leading to the generation of internally-deleted, but mostly functional, pseudodystrophin proteins with the potential to compensate for the genetic loss of dystrophin.
View Article and Find Full Text PDFAdv Biotechnol (Singap)
February 2024
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang, China.
Alternative splicing (AS) significantly enriches the diversity of transcriptomes and proteomes, playing a pivotal role in the physiology and development of eukaryotic organisms. With the continuous advancement of high-throughput sequencing technologies, an increasing number of novel transcript isoforms, along with factors related to splicing and their associated functions, are being unveiled. In this review, we succinctly summarize and compare the different splicing mechanisms across prokaryotes and eukaryotes.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of Medicine, Durham, NC, 27710, USA.
Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.
View Article and Find Full Text PDFGenes Dev
January 2025
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90095, USA;
The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing.
View Article and Find Full Text PDFCells Dev
January 2025
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, Querétaro, Querétaro, Mexico. Electronic address:
fos genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous GCN4 gene is required to mediate "emergency" situations like nutrient deprivation and the unfolded protein response.
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