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  • 1
    Publication Date: 2009-01-27
    Description: Genome-wide pervasive transcription has been reported in many eukaryotic organisms, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs or their generation itself. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3' ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals-that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766638/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766638/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Zhenyu -- Wei, Wu -- Gagneur, Julien -- Perocchi, Fabiana -- Clauder-Munster, Sandra -- Camblong, Jurgi -- Guffanti, Elisa -- Stutz, Francoise -- Huber, Wolfgang -- Steinmetz, Lars M -- P01 HG000205/HG/NHGRI NIH HHS/ -- P01 HG000205-19/HG/NHGRI NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- R01 GM068717-06/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Feb 19;457(7232):1033-7. doi: 10.1038/nature07728. Epub 2009 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19169243" target="_blank"〉PubMed〈/a〉
    Keywords: Gene Expression Profiling ; Gene Expression Regulation, Fungal/*genetics ; Genes, Fungal/genetics ; Genes, Overlapping/genetics ; Genome, Fungal/genetics ; Models, Genetic ; Nucleosomes ; Promoter Regions, Genetic/*genetics ; RNA Stability/genetics ; RNA, Fungal/*genetics ; RNA, Untranslated/genetics ; Saccharomyces cerevisiae/classification/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-04-26
    Description: Transcript function is determined by sequence elements arranged on an individual RNA molecule. Variation in transcripts can affect messenger RNA stability, localization and translation, or produce truncated proteins that differ in localization or function. Given the existence of overlapping, variable transcript isoforms, determining the functional impact of the transcriptome requires identification of full-length transcripts, rather than just the genomic regions that are transcribed. Here, by jointly determining both transcript ends for millions of RNA molecules, we reveal an extensive layer of isoform diversity previously hidden among overlapping RNA molecules. Variation in transcript boundaries seems to be the rule rather than the exception, even within a single population of yeast cells. Over 26 major transcript isoforms per protein-coding gene were expressed in yeast. Hundreds of short coding RNAs and truncated versions of proteins are concomitantly encoded by alternative transcript isoforms, increasing protein diversity. In addition, approximately 70% of genes express alternative isoforms that vary in post-transcriptional regulatory elements, and tandem genes frequently produce overlapping or even bicistronic transcripts. This extensive transcript diversity is generated by a relatively simple eukaryotic genome with limited splicing, and within a genetically homogeneous population of cells. Our findings have implications for genome compaction, evolution and phenotypic diversity between single cells. These data also indicate that isoform diversity as well as RNA abundance should be considered when assessing the functional repertoire of genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705217/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelechano, Vicent -- Wei, Wu -- Steinmetz, Lars M -- P01 HG000205/HG/NHGRI NIH HHS/ -- R01 GM068717/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 May 2;497(7447):127-31. doi: 10.1038/nature12121. Epub 2013 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23615609" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Fungal Proteins/genetics ; *Gene Expression Profiling ; Genes, Fungal/genetics ; Genome, Fungal/genetics ; Genomics ; Protein Isoforms/genetics ; RNA, Fungal/*analysis/*genetics ; RNA, Messenger/analysis/genetics ; Regulatory Sequences, Ribonucleic Acid/genetics ; Saccharomyces cerevisiae/*genetics ; Transcription, Genetic/*genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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