Building Knowledge About Alternatively-spliced Dual-Coding Exons

建立关于选择性剪接双编码外显子的知识

• 批准号: 10363514
• 负责人: Travis John Wheeler
• 金额: $ 23.93万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10363514
• 关键词: Alternative Splicing; Architecture; Atlases; Back; Binding Sites; Bioinformatics; Biological; Biology; Catalogs; Code; Collection; Computer software; Custom; Data; Data Set; Development; Eukaryota; Exons; Future; Genes; Human; Investigation; Knowledge; Light; Mass Spectrum Analysis; Messenger RNA; N-terminal; Nature; Nucleotides; Open Reading Frames; Pattern; Peptide Signal Sequences; Peptides; Play; Proteins; RNA Splicing; Reading Frames; Research; Role; Site; Specificity; Terminator Codon; Tissues; Variant; Visualization; Work; gene function; human tissue; insight; mouse genome; programs; repository; trait; transcriptome sequencing; web services; web-accessible

Abstract Most protein-coding genes in humans and other eukaryotes are made up of a collection of exons, which are concatenated to form the messenger RNA (mRNA) that encodes a final protein product. The well-known phenomenon of alternative splicing makes it possible for a single gene to encode multiple protein products, by conditionally including only a subset of the gene’s exons into the expressed mRNA. A more surprising mechanism for producing alternate protein products is to utilize an alternate reading frame of a standard exon, through aberrant splicing; using custom software built in our research group, we have found that this mechanism appears to be quite common. Specifically, ~13% of all human genes include at least one exon that conditionally encodes alternate peptides, and these “dual-coding exons” are highly-conserved: 98% correspond to homologous exons in the mouse genome that also encode two open reading frames. Light exploration has identified dozens of human genes that show tissue-specific patterns of reading frame usage, suggesting a functional role for at least some of these variants. Here, we describe a plan to (i) leverage massive public atlases of human tissue-specific and development-specific RNA-Seq and mass spectrometry data to tabulate the extent of differential use of these frame-shifted splicing variants, and to (ii) analyze the computationally-predicted structural and functional impact of dual-coding variants, and the sequence signals controlling them. The results of these analyses will be accumulated for release in an open and accessible web service.

摘要