Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Spealman P

PROVIDER: S-EPMC5793785 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Spealman Pieter P Naik Armaghan W AW May Gemma E GE Kuersten Scott S Freeberg Lindsay L Murphy Robert F RF McManus Joel J

Genome research 20171218 2

Upstream open reading frames (uORFs), located in transcript leaders (5' UTRs), are potent <i>cis</i>-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 ...[more]

PMID: 29254944

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Project description:Translational regulation plays an important role in protein synthesis. Dysregulation of translation causes abnormal cell physiology and leads to diseases such as inflammatory disorders and cancers. An emerging technique, called ribosome profiling (ribo-seq), was developed to capture a snapshot of translation. It is based on deep sequencing of ribosome-protected mRNA fragments. A lot of ribo-seq data have been generated in various studies, so databases are needed for depositing and visualizing the published ribo-seq data. Nowadays, GWIPS-viz, RPFdb and TranslatomeDB are the three largest databases developed for this purpose. However, two challenges remain to be addressed. First, GWIPS-viz and RPFdb databases align the published ribo-seq data to the genome. Since ribo-seq data aim to reveal the actively translated mRNA transcripts, there are advantages of aligning ribo-req data to the transcriptome over the genome. Second, TranslatomeDB does not provide any visualization and the other two databases only provide visualization of the ribo-seq data around a specific genomic location, while simultaneous visualization of the ribo-seq data on multiple mRNA transcripts produced from the same gene or different genes is desired. To address these two challenges, we developed the Human Ribosome Profiling Data viewer (HRPDviewer). HRPDviewer (i) contains 610 published human ribo-seq datasets from Gene Expression Omnibus, (ii) aligns the ribo-seq data to the transcriptome and (iii) provides visualization of the ribo-seq data on the selected mRNA transcripts. Using HRPDviewer, researchers can compare the ribosome binding patterns of multiple mRNA transcripts from the same gene or different genes to gain an accurate understanding of protein synthesis in human cells. We believe that HRPDviewer is a useful resource for researchers to study translational regulation in human.Database URL: http://cosbi4.ee.ncku.edu.tw/HRPDviewer/ or http://cosbi5.ee.ncku.edu.tw/HRPDviewer/.

Dataset Information

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

Publications

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

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