Integrated genomic analysis reveals key features of long undecoded transcript isoform-based gene repression.
Long undecoded transcript isoforms (LUTIs) represent a class of non-canonical mRNAs that downregulate gene expression through the combined act of transcriptional and translational repression. While single gene studies revealed important aspects of LUTI-based repression, how these features affect gene regulation on a global scale is unknown. Using transcript leader and direct RNA sequencing, here, we identify 74 LUTI candidates that are specifically induced in meiotic prophase. Translational repression of these candidates appears to be ubiquitous and is dependent on upstream open reading frames. However, LUTI-based transcriptional repression is variable. In only 50% of the cases, LUTI transcription causes downregulation of the protein-coding transcript isoform. Higher LUTI expression, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position are the strongest predictors of LUTI-based transcriptional repression. We conclude that LUTIs downregulate gene expression in a manner that integrates translational repression, chromatin state changes, and the magnitude of LUTI expression.
['Tresenrider|Amy|A|', 'Morse|Kaitlin|K|', 'Jorgensen|Victoria|V|', 'Chia|Minghao|M|', 'Liao|Hanna|H|', 'van Werven|Folkert Jacobus|FJ|', 'Ünal|Elçin|E|']
D002843:Chromatin D015966:Gene Expression Regulation, Fungal D017930:Genes, Reporter D023281:Genomics D008540:Meiosis D000081414:Nanopore Sequencing D009707:Nucleosomes D016366:Open Reading Frames D011401:Promoter Regions, Genetic D011418:Prophase D014176:Protein Biosynthesis D020033:Protein Isoforms D012333:RNA, Messenger D012441:Saccharomyces cerevisiae D014157:Transcription Factors D014158:Transcription, Genetic
isoform LUTI gene expression translation chromatin H3K36 differentiation meiosis transcription factor uORF