Noncanonical transcript forms in yeast and their regulation during environmental stress

Yoon, Oh Kyu; Brem, Rachel B.

doi:10.1261/rna.2038810

Cited by 71 publications

(79 citation statements)

References 85 publications

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“…1; Supplemental File 1A-D). We next mapped transcript leader sequences (TLSs) and 3 ′ UTRs genome-wide for each of the four species using high-throughput sequencing approaches, TL-seq (Arribere and Gilbert 2013) and pA-seq (Yoon and Brem 2010). We identified significant (false discovery rate [FDR] < 0.001) (Methods) transcription start sites (TSSs) and polyadenylation sites (pAs) in all four species (Supplemental File 1A-D).…”

Section: Resultsmentioning

confidence: 99%

“…High-throughput sequencing library preparation 5 ′ and 3 ′ end mapping libraries were prepared as previously described (Yoon and Brem 2010;Arribere and Gilbert 2013;Supplemental Materials). Using Bowtie (Langmead et al 2009) default parameters, 5 ′ -and 3 ′ -end reads were aligned to corresponding genomes and converted to single nucleotide read-end pileups.…”

Section: Methodsmentioning

confidence: 99%

“…Transcript leader lengths from our S. cerevisiae strain (S288C) were significantly longer than those of other species (Wilcoxon The genomes of nonmodel species were reannotated to include ncRNA and correct previous errors, resulting in changes to ∼20% of genes on average (Methods). (B) Transcript leaders and polyadenylation sites were annotated for four Saccharomyces sensu stricto species using TL-seq (Arribere and Gilbert 2013) and pA-seq (Yoon and Brem 2010). TL-seq and pA-seq peaks were trend filtered for FDR control (β = 0.001) and evaluated for their usage frequency.…”

Section: Evolutionary Comparisons Of Yeast Transcript Leadersmentioning

confidence: 99%

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Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

et al. 2017

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Upstream open reading frames (uORFs), located in transcript leaders (5′ UTRs), are potent cis-acting regulators of translation and mRNA turnover. Recent genome-wide ribosome profiling studies suggest that thousands of uORFs initiate with non-AUG start codons. Although intriguing, these non-AUG uORF predictions have been made without statistical control or validation; thus, the importance of these elements remains to be demonstrated. To address this, we took a comparative genomics approach to study AUG and non-AUG uORFs. We mapped transcription leaders in multiple Saccharomyces yeast species and applied a novel machine learning algorithm (uORF-seqr) to ribosome profiling data to identify statistically significant uORFs. We found that AUG and non-AUG uORFs are both frequently found in Saccharomyces yeasts. Although most non-AUG uORFs are found in only one species, hundreds have either conserved sequence or position within Saccharomyces. uORFs initiating with UUG are particularly common and are shared between species at rates similar to that of AUG uORFs. However, non-AUG uORFs are translated less efficiently than AUG-uORFs and are less subject to removal via alternative transcription initiation under normal growth conditions. These results suggest that a subset of non-AUG uORFs may play important roles in regulating gene expression.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Evolutionary Comparisons Of Yeast Transcript Leadersmentioning

confidence: 99%

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Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

et al. 2017

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“…Alternative splicing, alternative polyadenylation or alternative cleavage site selection mechanisms may be involved (Pauws et al, 2001;Licatalosi & Darnell 2010;Proudfoot, 2011). Alternative splicing and RNA shortening have been recently reported in cancer cell lines and upon cellular stress, and it has been proposed that 3'UTR variants provide a way to escape microRNA regulation (Mayr & Bartel 2009;Dutertre et al, 2011) or influence mRNA stability (Yoon and Brem, 2010).…”

Section: Discussionmentioning

confidence: 99%

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome

Galloni¹

2012

Int. J. Dev. Biol.

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Stem cells are the closest relatives of the totipotent primordial cell, which is able to spawn millions of daughter cells and hundreds of cell types in multicellular organisms. Stem cells are involved in tissue homeostasis and regeneration, and may play a major role in cancer development. Among animals, planarians host a model stem cell type, called the neoblast, which essentially confers immortality. Gaining insights into the global transcriptional landscape of these exceptional cells takes an unprecedented turn with the advent of Next Generation Sequencing methods. Two Digital Gene Expression transcriptomes of Schmidtea mediterranea planarians, with or without neoblasts lost through irradiation, were produced and analyzed. Twenty one bp NlaIII tags were mapped to transcripts in the Schmidtea and Dugesia taxids. Differential representation of tags in normal versus irradiated animals reflects differential gene expression. Canonical and non-canonical tags were included in the analysis, and comparative studies with human orthologs were conducted. Transcripts fell into 3 categories: invariant (including housekeeping genes), absent in irradiated animals (potential neoblast-specific genes, IRDOWN) and induced in irradiated animals (potential cellular stress response, IRUP). Different mRNA variants and gene family members were recovered. In the IRDOWN class, almost all of the neoblast-specific genes previously described were found. In irradiated animals, a larger number of genes were induced rather than lost. A significant fraction of IRUP genes behaved as if transcript versions of different lengths were produced. Several novel potential neoblast-specific genes have been identified that varied in relative abundance, including highly conserved as well as novel proteins without predicted orthologs. Evidence for a large body of antisense transcripts, for example regulated antisense for the Smed-piwil1 gene, and evidence for RNA shortening in irradiated animals is presented. Novel neoblast-specific candidates include a peroxiredoxin protein that appears to be preferentially expressed in human embryonic stem cells.

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“…Recent RNA-seq experiments identified widespread changes in 39 end length in yeast (Yoon and Brem 2010). Interestingly, their examination of dithiothreitol (DTT) stress revealed numerous alternative polyadenylation events that result in truncation within the coding region.…”

Section: Plasticity Of Transcript Architecture During Meiosismentioning

confidence: 99%

Meiosis-induced alterations in transcript architecture and noncoding RNA expression in S. cerevisiae

Guisbert

Zhang²,

Flatow³

et al. 2012

RNA

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Changes in transcript architecture can have powerful effects on protein expression. Regulation of the transcriptome is often dramatically revealed during dynamic conditions such as development. To examine changes in transcript architecture we analyzed the expression and transcript boundaries of protein-coding and noncoding RNAs over the developmental process of meiosis in Saccharomyces cerevisiae. Custom-designed, high-resolution tiling arrays were used to define the time-resolved transcriptome of cells undergoing meiosis and sporulation. These arrays were specifically designed for the S. cerevisiae strain SK1 that sporulates with high efficiency and synchrony. In addition, new methods were created to define transcript boundaries and to identify dynamic changes in transcript expression and architecture over time. Of 8407 total segments, 699 (8.3%) were identified by our algorithm as regions containing potential transcript architecture changes. Our analyses reveal extensive changes to both the coding and noncoding transcriptome, including altered 59 ends, 39 ends, and splice sites. Additionally, 3910 (46.5%) unannotated expressed segments were identified. Interestingly, subsets of unannotated RNAs are located across from introns (anti-introns) or across from the junction between two genes (anti-intergenic junctions). Many of these unannotated RNAs are abundant and exhibit sporulation-specific changes in expression patterns. All work, including heat maps of the tiling array, annotation for the SK1 strain, and phastCONS conservation analysis, is available at http://groups.molbiosci.northwestern. edu/sontheimer/sk1meiosis.php. Our high-resolution transcriptome analyses reveal that coding and noncoding transcript architectures are exceptionally dynamic in S. cerevisiae and suggest a vast array of novel transcriptional and post-transcriptional control mechanisms that are activated upon meiosis and sporulation.

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Noncanonical transcript forms in yeast and their regulation during environmental stress

Cited by 71 publications

References 85 publications

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

Conserved non-AUG uORFs revealed by a novel regression analysis of ribosome profiling data

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome

Meiosis-induced alterations in transcript architecture and noncoding RNA expression in S. cerevisiae

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