Nonsense codons that prematurely terminate translation generate potentially deleterious truncated proteins. Here, we show that the T cell receptor-beta (TCRbeta) gene, which acquires in-frame nonsense codons at high frequency during normal lymphocyte development, gives rise to an alternatively spliced transcript [alternative messenger RNA (alt-mRNA)] that skips the offending mutations that generate such nonsense codons. This alt-mRNA is up-regulated by a transfer RNA-dependent scanning mechanism that responds specifically to mutations that disrupt the reading frame. The finding that translation signals regulate the levels of alternatively spliced mRNAs generated in the nucleus may alter the current view of how gene expression is controlled in eukaryotic cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.1069757 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NUMB alternative splicing and isoform specific functions in development and disease.
J Biol Chem
January 2025
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:
The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.
View Article and Find Full Text PDFNutrient control of splice site selection contributes to methionine addiction of cancer.
Mol Metab
January 2025
Department of Biological Chemistry, University of California, Irvine School of Medicine. Electronic address:
Objectives: Many cancer cells depend on exogenous methionine for proliferation, whereas non-tumorigenic cells can divide in media supplemented with the metabolic precursor homocysteine. This phenomenon is known as methionine dependence of cancer or methionine addiction. The underlying mechanisms driving this cancer-specific metabolic addiction are poorly understood.
View Article and Find Full Text PDFA Series of Novel Alleles of Modulating Heading and Salt Tolerance in Rice.
Plants (Basel)
January 2025
State Key Laboratory of Rice Biology and Breeding, China National Center for Rice Improvement, China National Rice Research Institute, Hangzhou 311400, China.
Rice ( L.) is a staple crop for nearly half of the global population and one of China's most extensively cultivated cereals. Heading date, a critical agronomic trait, determines the regional and seasonal adaptability of rice varieties.
View Article and Find Full Text PDFCircular RNA Formation and Degradation Are Not Directed by Universal Pathways.
Int J Mol Sci
January 2025
Department of Rare Diseases, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Circular RNAs (circRNAs) are a class of unique transcripts characterized by a covalently closed loop structure, which differentiates them from conventional linear RNAs. The formation of circRNAs occurs co-transcriptionally and post-transcriptionally through a distinct type of splicing known as back-splicing, which involves the formation of a head-to-tail splice junction between a 5' splice donor and an upstream 3' splice acceptor. This process, along with exon skipping, intron retention, cryptic splice site utilization, and lariat-driven intron processing, results in the generation of three main types of circRNAs (exonic, intronic, and exonic-intronic) and their isoforms.
View Article and Find Full Text PDFImpact of Larval Sertraline Exposure on Alternative Splicing in Neural Tissue of Adult .
Int J Mol Sci
January 2025
Immunology Laboratory (UMF), Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Barrios No. 1, Los Reyes Iztacala, Tlalnepantla 54090, Mexico.
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat various psychiatric disorders such as depression and anxiety due to its ability to increase serotonin availability in the brain. Recent findings suggest that sertraline may also influence the expression of genes related to synaptic plasticity and neuronal signaling pathways. Alternative splicing, a process that allows a single gene to produce multiple protein isoforms, plays a crucial role in the regulation of neuronal functions and plasticity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!