Transcriptional neighborhoods regulate transcript isoform lengths and expression levels

Autor:	Aaron N. Brooks, Amanda L. Hughes, Sandra Clauder-Münster, Leslie A. Mitchell, Jef D. Boeke, Lars M. Steinmetz
Rok vydání:	2022
Předmět:	Gene Rearrangement Multidisciplinary Base Sequence Transcription Genetic Sequence Analysis RNA Genetic Variation RNA Fungal Saccharomyces cerevisiae Article Alternative Splicing Protein Isoforms RNA Messenger RNA-Seq Genome Fungal Transcriptome 3' Untranslated Regions
Zdroj:	Science
ISSN:	1095-9203
Popis:	Sequence features of genes and their flanking regulatory regions are determinants of RNA transcript isoform expression and have been used as context-independent plug-and-play modules in synthetic biology. However, genetic context—including the adjacent transcriptional environment—also influences transcript isoform expression levels and boundaries. We used synthetic yeast strains with stochastically repositioned genes to systematically disentangle the effects of sequence and context. Profiling 120 million full-length transcript molecules across 612 genomic perturbations, we observed sequence-independent alterations to gene expression levels and transcript isoform boundaries that were influenced by neighboring transcription. We identified features of transcriptional context that could predict these alterations and used these features to engineer a synthetic circuit where transcript length was controlled by neighboring transcription. This demonstrates how positional context can be leveraged in synthetic genome engineering.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebbd9d84828be521276ef4238830ea65 https://pubmed.ncbi.nlm.nih.gov/35314808 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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