title: Alternatively spliced TCR mRNA induced by disruption of reading frame.
abstract: 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.
authors.affiliation: Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Box 180, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: John I
authors.initials: JI
authors.lastname: Hamilton
authors.forename: Mark S
authors.initials: MS
authors.lastname: Carter
authors.forename: Shulin
authors.initials: S
authors.lastname: Li
authors.forename: Miles F
authors.initials: MF
authors.lastname: Wilkinson
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D018389:Codon, Nonsense; D004742:Enhancer Elements, Genetic; D005091:Exons; D016368:Frameshift Mutation; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D051379:Mice; D020125:Mutation, Missense; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016364:Reading Frames; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta