Regulatory and evolutionary footprints of messenger RNA secondary structure in primate transcriptomes
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ABSTRACT:
PROVIDER: PRJNA246200 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1270150.fastq.gz | Fastqsanger.gz | |||
| SRR1270160.fastq.gz | Fastqsanger.gz | |||
| SRR1270170.fastq.gz | Fastqsanger.gz | |||
| SRR1270180.fastq.gz | Fastqsanger.gz | |||
| SRR1270151.fastq.gz | Fastqsanger.gz |
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Project description:Messenger RNA secondary structure is critical to all aspects of post-transcriptional regulation. However, the global regulatory and evolutionary significance of mRNA secondary structure remains largely illusive. Here, we describe a transcriptome-wide analysis of RNA secondary structure in humans and two non-human primates, based on a high-throughput, nuclease-mediated, structure mapping approach. Using this methodology, we uncover global patterns of mRNA secondary structure, which we find to be conserved through primate evolution. We provide evidence for secondary structure-based regulatory pathways, which impact on gene expression through associations with translational machinery and RNA-binding proteins, including components of the microprocessor complex. Our results lend support to an unexpected, conserved mechanism by which highly structured regions of mRNAs serve as processing sites for small RNAs, resulting in subsequent turnover. Global mRNA secondary structure analysis in primate transcriptomes using high-throughput, nuclease-mediated, structure mappinng approaches of dsRNA-seq and ssRNA-seq, also with polyA+ mRNA-seq, smRNA-seq (small RNA), and genome-wide mapping of uncapped and cleaved transcripts (GMUCT); these NGS-seq experiments were carried out in three primate brains as well as three different cell lines, both in in vitro and in vivo.
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Project description:Messenger RNA secondary structure is critical to all aspects of post-transcriptional regulation. However, the global regulatory and evolutionary significance of mRNA secondary structure remains largely illusive. Here, we describe a transcriptome-wide analysis of RNA secondary structure in humans and two non-human primates, based on a high-throughput, nuclease-mediated, structure mapping approach. Using this methodology, we uncover global patterns of mRNA secondary structure, which we find to be conserved through primate evolution. We provide evidence for secondary structure-based regulatory pathways, which impact on gene expression through associations with translational machinery and RNA-binding proteins, including components of the microprocessor complex. Our results lend support to an unexpected, conserved mechanism by which highly structured regions of mRNAs serve as processing sites for small RNAs, resulting in subsequent turnover.
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Project description:Induced pluripotent stem cells (iPSCs) are regarded as a central tool to understand human biology in health and disease. Similarly, iPSCs from closely related species should be a central tool to understand human evolution and to identify conserved and variable patterns of iPSC disease models. Here, we have generated human, gorilla, bonobo and cynomolgus monkey iPSCs. We show that these cells are well comparable in their differentiation potential and generally similar to human, cynomolgus and rhesus monkey embryonic stem cells (ESCs). RNA sequencing reveals that expression differences among clones, individuals and stem cell type are all of very similar magnitude within a species. In contrast, expression differences between closely related primate species are three times larger and most genes show significant expression differences among the analysed species. However, pseudogenes differ more than twice as much, suggesting that evolution of expression levels in primate stem cells is rapid, but constrained. These patterns in pluripotent stem cells are comparable to those found in other tissues except testis. Hence, primate iPSCs reveal insights into general primate gene expression evolution and should provide a rich source to identify conserved and species-specific gene expression patterns for cellular phenotypes. Contributors: Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany We used expression profiling to characterize five gorilla, two bonobo and three macaque iPS clones as well as three iPS clones from two human individuals, three human embryonic stem (ES) cell lines and three macaque ES cell lines. We generated tagged RNA-Seq libraries from these 19 samples including four technical replicates (23 samples). Over 100 million single end reads were generated on the Illumina platform.
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