Small RNA expression and strain specificity in the rat
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE19054 | GEO | 2010/02/17
SECONDARY ACCESSION(S): PRJNA120555
REPOSITORIES: GEO
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Project description:Background Digital gene expression (DGE) profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR) from six different rat tissues (spleen, liver, brain, testis, heart, kidney). We describe the expression patterns of known and novel micro (mi)RNAs and piwi-interacting (pi)RNAs. We confirmed the expression of 589 known miRNAs and identified 56 miRNAs homologous to known human or mouse miRNAs, as well as 45 new rat miRNAs. Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. In accordance with earlier findings, we observed a highly tissue-specific expression pattern for all tissues analyzed. The brain was found to express the highest number of tissue-specific miRNAs, followed by testis. Notably, our experiments also revealed robust strain-specific differential miRNA expression in the liver that is caused by genetic variation between the strains. Finally, we identified two types of germline-specific piRNAs in testis, mapping either to transposons or in strand-specific clusters. Taken together, the small RNA compendium described here advances the annotation of small RNAs in the rat genome. Strain and tissue-specific expression patterns furthermore provide a strong basis for studying the role of small RNAs in regulatory networks as well as biological process like physiology and neurobiology that are extensively studied in this model system. Small RNAs from 6 tissues were cloned and sequenced. Tissues included whole brain, liver, spleen, heart, testis, kidney. Tissues were sequenced from 2 rats: one BN-Lx rat and one SHR rat. For strain-specific miRNA expression we included 4 replicate whole livers, i.e. from 2 BN-Lx rats and 2 SHR rats.
2010-02-17 | E-GEOD-19054 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small regulatory RNAs that derive from distinctive hairpin transcripts. To learn more about the miRNAs of mammals, we sequenced 60 million small RNAs from mouse brain, ovary, testes, embryonic stem cells, three embryonic stages, and whole newborns. Analysis of these sequences confirmed 387 annotated miRNA genes and identified 110 novel miRNA genes. Over 150 previously annotated miRNAs and hundreds of candidates failed to yield sequenced RNAs with miRNA-like features. Ectopically expressing these previously proposed miRNA hairpins also did not yield small RNAs, whereas ectopically expressing the confirmed and newly identified hairpins usually did yield small RNAs with the classical miRNA features, including dependence on the Drosha endonuclease for processing. These experiments, which suggest that previous estimates of conserved mammalian miRNAs were inflated, provide a substantially revised list of confidently identified mammalian miRNAs from which to infer the general features of mammalian miRNAs. Our analyses also revealed new aspects of miRNA biogenesis and modification, including tissue-specific strand preferences, sequential Dicer cleavage of a metazoan pre-miRNA, newly identified instances of miRNA editing, and evidence for widespread Lin28-like miRNA regulation. For miRNA discovery, small RNAs were sequenced from mouse brain, ovary, testes, three embryonic stages, and whole newborns; for ectopic over-expression assays, pre-miRNA hairpins and the surrounding regions were transfected into HEK293T, and the small RNA were sequenced from the transfected cells 39-48 hours after transfection.
2010-04-26 | E-GEOD-20384 | biostudies-arrayexpress
Project description:Small non-coding RNAs play important roles in regulating gene expression during development and disease. However, a comprehensive analysis of small RNAs in developing brain is largely lacking. By using next-generation sequencing technique, we carried out a systematic analysis of small RNA transcriptome of rat neocortex from early developmental stage till adult. Our results revealed an extraordinary degree of stage-specific profiling of miRNA, and other classes of small RNAs including snoRNA, rasRNA, scRNA and unexpectedly piRNA, which was considered to be solely expressed in germline tissues. Developmentally regulated miRNA editing was also observed. This study further showed the effectiveness of the high through-put sequencing in genome-wide analysis of small RNAs. The dataset described here will greatly contribute to our understanding of the divergence, variation, and function of small RNAs and may be a valuable resource in clarifying new regulatory mechanisms of cortical development. Identification and quantification of small RNA: forebrain and cortex from E10 to P28
2012-06-25 | E-GEOD-27576 | biostudies-arrayexpress
Project description:RNA-editing is a tightly regulated, and essential cellular process for a properly functioning brain. Dysfunction of A-to-I RNA editing can have catastrophic effects, particularly in the central nervous system. Thus, understanding how the process of RNA-editing is regulated has important implications for human health. However, at present, very little is known about the regulation of editing across tissues, and individuals. Here we present an analysis of RNA-editing patterns from 9 different tissues harvested from a single mouse. For comparison, we also analyzed data for 5 of these tissues harvested from 15 additional animals. We find that tissue specificity of editing largely reflects differential expression of substrate transcripts across tissues. We identified a surprising enrichment of editing in intronic regions of brain transcripts, that could account for previously reported higher levels of editing in brain. There exists a small but remarkable amount of editing which is tissue-specific, despite comparable expression levels of the edit site across multiple tissues. Expression levels of editing enzymes and their isoforms can explain some, but not all of this variation. Together, these data suggest a complex regulation of the RNA-editing process beyond transcript expression levels. Tissues include: brain, heart, kidney, liver, lung, skin, spleen, testis, thymus mRNA profiles of 9 tissues from an 8 week old, male C57BL/6 mouse were generated by deep sequencing using Illumina HiSeq.
2016-01-19 | E-GEOD-74747 | biostudies-arrayexpress
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs. Examination of the effect of ADAR2 on gene expression in mature mouse wildtype and ADAR2 knockout brain using AffymetrixM-BM-. GeneChipM-BM-. Whole Transcript (WT) Expression Arrays (Analysis by KFB Regensburg, Germany)
2014-10-02 | E-GEOD-61067 | biostudies-arrayexpress
Project description:Small non-coding RNAs play important roles in regulating gene expression during development and disease. However, a comprehensive analysis of small RNAs in developing brain is largely lacking. By using next-generation sequencing technique, we carried out a systematic analysis of small RNA transcriptome of rat neocortex from early developmental stage till adult. Our results revealed an extraordinary degree of stage-specific profiling of miRNA, and other classes of small RNAs including snoRNA, rasRNA, scRNA and unexpectedly piRNA, which was considered to be solely expressed in germline tissues. Developmentally regulated miRNA editing was also observed. This study further showed the effectiveness of the high through-put sequencing in genome-wide analysis of small RNAs. The dataset described here will greatly contribute to our understanding of the divergence, variation, and function of small RNAs and may be a valuable resource in clarifying new regulatory mechanisms of cortical development.
2012-06-26 | GSE27576 | GEO
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs. Examination of the effect of ADAR2 on mature miRNA abundance and sequence in adult mouse brain.
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2010-04-26 | GSE20384 | GEO
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