A genome-wide map of circular RNAs in adult zebrafish (original) (raw)
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Dynamic Expression of Long Non-Coding RNAs (lncRNAs) in Adult Zebrafish
PLoS ONE, 2013
Long non-coding RNAs (lncRNA) represent an assorted class of transcripts having little or no protein coding capacity and have recently gained importance for their function as regulators of gene expression. Molecular studies on lncRNA have uncovered multifaceted interactions with protein coding genes. It has been suggested that lncRNAs are an additional layer of regulatory switches involved in gene regulation during development and disease. LncRNAs expressing in specific tissues or cell types during adult stages can have potential roles in form, function, maintenance and repair of tissues and organs. We used RNA sequencing followed by computational analysis to identify tissue restricted lncRNA transcript signatures from five different tissues of adult zebrafish. The present study reports 442 predicted lncRNA transcripts from adult zebrafish tissues out of which 419 were novel lncRNA transcripts. Of these, 77 lncRNAs show predominant tissue restricted expression across the five major tissues investigated. Adult zebrafish brain expressed the largest number of tissue restricted lncRNA transcripts followed by cardiovascular tissue. We also validated the tissue restricted expression of a subset of lncRNAs using independent methods. Our data constitute a useful genomic resource towards understanding the expression of lncRNAs in various tissues in adult zebrafish. Our study is thus a starting point and opens a way towards discovering new molecular interactions of gene expression within the specific adult tissues in the context of maintenance of organ form and function.
zflncRNApedia: A Comprehensive Online Resource for Zebrafish Long Non-Coding RNAs
PloS one, 2015
Recent transcriptome annotation using deep sequencing approaches have annotated a large number of long non-coding RNAs in zebrafish, a popular model organism for human diseases. These studies characterized lncRNAs in critical developmental stages as well as adult tissues. Each of the studies has uncovered a distinct set of lncRNAs, with minor overlaps. The availability of the raw RNA-Seq datasets in public domain encompassing critical developmental time-points and adult tissues provides us with a unique opportunity to understand the spatiotemporal expression patterns of lncRNAs. In the present report, we created a catalog of lncRNAs in zebrafish, derived largely from the three annotation sets, as well as manual curation of literature to compile a total of 2,267 lncRNA transcripts in zebrafish. The lncRNAs were further classified based on the genomic context and relationship with protein coding gene neighbors into 4 categories. Analysis revealed a total of 86 intronic, 309 promoter a...
Identification and characterization of circular RNAs in zebrafish
FEBS Letters, 2016
Circular RNAs (circRNAs) play critical roles in signal transduction during cell proliferation, differentiation, and apoptosis in a posttranscriptional manner. Recently, circRNAs have been proved to be a large class of animal RNAs with regulatory potency. However, whether circRNAs can respond to mechanical force (MF) and impact on human periodontal ligament stem cells (PDLSCs) and the orthodontic tooth movement (OTM) process remain unknown. Here, we investigated the circRNAs expression patterns in PDLSCs induced by MF and found that circRNAs were responsive to the MF in PDLSCs. Through the valid reads' distribution analysis, we found that the majority of reads in both the control PDLSCs and the MF-induced PDLSCs were distributed in exons. Then we analyzed Gene Ontology terms of genes that overlap with or are neighbors of the stress-responsive circRNAs and found unique enrichment patterns in biological processes, molecular function, and cellular component of PDLSCs. Next, we predicted the possible functions of circRNAs through circRNAs-miRNAs networks. We found that one circRNA may regulate one or several miRNA/miRNAs and one miRNA may interact with one or multiple circRNA/circRNAs. Importantly, a number of circRNAs were predicted to directly or indirectly regulate miRNAs-mediated osteogenic differentiation in mesenchymal stem cells. For instance, circRNA3140 was highly and widely associated with microRNA-21, which plays a critical role in MF-induced osteogenic differentiation of PDLSCs. Taken together, these findings reveal a previously unrecognized mechanism that MF can induce the expression changes of circRNAs in PDLSCs, which may modulate the OTM process and the alveolar bone remodeling.
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis
Genome Research, 2012
Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time-series of RNA-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.
Function of Circular RNAs in Fish and Their Potential Application as Biomarkers
International Journal of Molecular Sciences, 2021
Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.
Short Stories on Zebrafish Long Noncoding RNAs
Zebrafish, 2014
The recent re-annotation of the transcriptome of human and other model organisms, using next-generation sequencing approaches, has unravelled a hitherto unknown repertoire of transcripts that do not have a potential to code for proteins. These transcripts have been largely classified into an amorphous class popularly known as long noncoding RNAs (lncRNA). This discovery of lncRNAs in human and other model systems have added a new layer to the understanding of gene regulation at the transcriptional and post-transcriptional levels. In recent years, three independent studies have discovered a number of lncRNAs expressed in different stages of zebrafish development and adult tissues using a high-throughput RNA sequencing approach, significantly adding to the repertoire of genes known in zebrafish. A subset of these transcripts also shows distinct and specific spatiotemporal patterns of gene expression, pointing to a tight regulatory control and potential functional roles in development, organogenesis, and/ or homeostasis. This review provides an overview of the lncRNAs in zebrafish and discusses how their discovery could provide new insights into understanding biology, explaining mutant phenotypes, and helping in potentially modeling disease processes.
RNA secondary structure profiling in zebrafish reveals unique regulatory features
BMC genomics, 2018
RNA is known to play diverse roles in gene regulation. The clues for this regulatory function of RNA are embedded in its ability to fold into intricate secondary and tertiary structure. We report the transcriptome-wide RNA secondary structure in zebrafish at single nucleotide resolution using Parallel Analysis of RNA Structure (PARS). This study provides the secondary structure map of zebrafish coding and non-coding RNAs. The single nucleotide pairing probabilities of 54,083 distinct transcripts in the zebrafish genome were documented. We identified RNA secondary structural features embedded in functional units of zebrafish mRNAs. Translation start and stop sites were demarcated by weak structural signals. The coding regions were characterized by the three-nucleotide periodicity of secondary structure and display a codon base specific structural constrain. The splice sites of transcripts were also delineated by distinct signature signals. Relatively higher structural signals were ob...
PLOS Computational Biology, 2020
Over the past two decades, researchers have discovered a special form of alternative splicing that produces a circular form of RNA. Although these circular RNAs (circRNAs) have garnered considerable attention in the scientific community for their biogenesis and functions, the focus of current studies has been on the tissue-specific circRNAs that exist only in one tissue but not in other tissues or on the disease-specific circRNAs that exist in certain disease conditions, such as cancer, but not under normal conditions. This approach was conducted in the relative absence of methods that analyze a group of common circRNAs that exist in both conditions, but are more abundant in one condition relative to another (differentially expressed). Studies of differentially expressed circRNAs (DECs) between two conditions would serve as a significant first step in filling this void. Here, we introduce a novel computational tool, seekCRIT (seek for differentially expressed CircRNAs In Transcriptome), that identifies the DECs between two conditions from high-throughput sequencing data. Using rat retina RNA-seq data from ischemic and normal conditions, we show that over 74% of identifiable circRNAs are expressed in both conditions and over 40 circRNAs are differentially expressed between two conditions. We also obtain a high qPCR validation rate of 90% for DECs with a FDR of < 5%. Our results demonstrate that seekCRIT is a novel and efficient approach to detect DECs using rRNA depleted RNA-seq data.
Deep sequencing of small RNA facilitates tissue and sex specific microRNA discovery in zebrafish
2015
Role of microRNAs in gene regulation has been well established. Though the number of genes appear to be equal between human and zebrafish, miRNAs detected in zebrafish (~247) is significantly low compared to human (~2000; miRBase Release 19). It appears that most of the miRNAs in zebrafish are yet to be discovered. Using next generation sequencing technology, we sequenced small RNAs from brain, gut, liver, ovary, testis, eye, heart and embryo of zebrafish. In few tissues (brain, gut, liver) sequencing was done sex specifically. About 16-62% of the sequenced reads mapped to known miRNAs of zebrafish, with the exceptions of ovary (5.7%) and testis (7.8%). We used miRDeep2, the miRNA predication tool, to discover the novel miRNAs using the un-annotated reads that ranged from 7.6 to 23.0%, with exceptions of ovary (51.4%) and testis (55.2%) that had the largest pool of un-annotated reads. The prediction tool identified a total of 459 novel pre-miRNAs. Comparison of miRNA expression data...