Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterize HOXA-AS3 and HOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar orthologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon. Functionally, the RNA products of HOXA-AS3 and HOXB-AS3 regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.

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Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

10.1101/2020.11.03.366716 ◽

2020 ◽

Author(s):

Neta Degani ◽

Elena Ainbinder ◽

Igor Ulitsky

Keyword(s):

Early Development ◽

Regulatory Networks ◽

Sequence Similarity ◽

Expression Patterns ◽

Embryonic Stem ◽

Vertebrate Lineage ◽

Protein Coding ◽

Cis Acting ◽

Central Regions ◽

Hox Clusters

AbstractLong noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterize HOXA-AS3 and HOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar homologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon, and their co-regulation by the CDX1/2 transcription factors. Functionally, the RNA products of HOXA-AS3 and HOXB-AS3 regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.

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Retroviral Transcriptional Regulation and Embryonic Stem Cells: War and Peace

Molecular and Cellular Biology ◽

10.1128/mcb.01293-14 ◽

2014 ◽

Vol 35 (5) ◽

pp. 770-777 ◽

Cited By ~ 63

Author(s):

Sharon Schlesinger ◽

Stephen P. Goff

Keyword(s):

Dna Sequences ◽

Regulatory Networks ◽

Es Cells ◽

Expression Patterns ◽

Embryonic Stem ◽

Cell Types ◽

Endogenous Retroviruses ◽

Regulatory Sequences ◽

Cellular Genes ◽

Wide Range

Retroviruses have evolved complex transcriptional enhancers and promoters that allow their replication in a wide range of tissue and cell types. Embryonic stem (ES) cells, however, characteristically suppress transcription of proviruses formed after infection by exogenous retroviruses and also of most members of the vast array of endogenous retroviruses in the genome. These cells have unusual profiles of transcribed genes and are poised to make rapid changes in those profiles upon induction of differentiation. Many of the transcription factors in ES cells control both host and retroviral genes coordinately, such that retroviral expression patterns can serve as markers of ES cell pluripotency. This overlap is not coincidental; retrovirus-derived regulatory sequences are often used to control cellular genes important for pluripotency. These sequences specify the temporal control and perhaps “noisy” control of cellular genes that direct proper cell gene expression in primitive cells and their differentiating progeny. The evidence suggests that the viral elements have been domesticated for host needs, reflecting the wide-ranging exploitation of any and all available DNA sequences in assembling regulatory networks.

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Networks of enhancers and microRNAs drive variation in cell states

10.1101/668145 ◽

2019 ◽

Author(s):

Meenakshi Chakraborty ◽

Sofia Hu ◽

Marco Del Giudice ◽

Andrea De Martino ◽

Carla Bosia ◽

...

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Feedback Loop ◽

Embryonic Stem ◽

Developmental Expression ◽

Protein Coding ◽

Pluripotency Factors ◽

Gene Regulatory ◽

Cell Variation ◽

Pluripotency Genes

AbstractCell-to-cell variation in gene expression is a common feature of developmental processes. Yet, it remains unclear whether molecular mediators can generate variation and how this process is coordinated across loci to allow the emergence of new cell states. Using embryonic stem cells (ESCs) as a model of development, we found interconverting cell states that resemble developmental expression programs and vary in activity at specific enhancers, such as those regulating pluripotency genes Nanog and Sox2 but not Pou5f1 (Oct4). Variable enhancers drive expression of variable genes, including those encoding microRNAs (miRNAs). Notably, variable miRNAs increase cell-to-cell variation by acting on neighborhoods of pluripotency genes. The encoded, variable pluripotency factors bind variable enhancers, forming a feedback loop that amplifies variation and allows the emergence of new cell states. These findings suggest gene regulatory networks composed of enhancers, protein-coding genes, and miRNAs harness inherent variation into developmental outcomes.

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Genome-Wide Identification and Characterization of the FAR1/FHY3 Family in Populus trichocarpa Torr. & Gray and Expression Analysis in Light Response

Forests ◽

10.3390/f12101385 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1385

Author(s):

Jiujun Du ◽

Lei Zhang ◽

Xiaolan Ge ◽

Xiaodong Xiang ◽

Demei Cao ◽

...

Keyword(s):

Regulatory Networks ◽

Higher Plants ◽

Populus Trichocarpa ◽

Expression Patterns ◽

Light Response ◽

Cis Acting ◽

Poplar Genome ◽

Genome Wide ◽

Identification And Characterization

Light is an important environmental factor for plant growth, and in higher plants, phytochrome A (phyA) is the predominant far-red photoreceptor, involved in various photoresponses. The FAR1/FHY3 transcription factor family, derived from transposases, is able to regulate plant development in response to multiple photosensitizers phytochrome. In total, 51 PtrFRSs were identified in the poplar genome, and were divided into 4 subfamilies. Among them, 47 PtrFRSs are located on 17 chromosomes. Upstream cis-acting elements of the PtrFRS genes were classified into three categories: growth and metabolism, stress and hormone, and the hormone and stress categories contained most of the cis-acting elements. Analysis of the regulatory networks and expression patterns showed that most PtrFRSs responded to changes in light intensity and were involved in the regulation of phytochromes. In this study, 51 PtrFRSs were identified and comprehensively bioinformatically analyzed, and preliminary functional analysis and prediction of PtrFRSs was carried out.

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MicroRNA Profiling: From Dark Matter to White Matter, or Identifying New Players in Neurobiology

The Scientific World JOURNAL ◽

10.1100/tsw.2007.201 ◽

2007 ◽

Vol 7 ◽

pp. 155-166 ◽

Cited By ~ 42

Author(s):

Anna M. Krichevsky

Keyword(s):

Dark Matter ◽

Mirna Expression ◽

Regulatory Networks ◽

Expression Patterns ◽

Basic Principles ◽

Protein Coding ◽

Rna Molecules ◽

Coding Regions ◽

Small Regulatory Rna ◽

Mirna Expression Profiling

Contemporary biology has been revolutionized by a recently discovered class of small regulatory RNA molecules, microRNAs (miRNAs). Missed by researchers for decades due to their tiny size, usually mapping to non-protein-coding regions of genomes, miRNAs and miRNA-mediated regulatory networks have been the “dark matter” of molecular biology. Deciphering miRNA pathways and functions in the CNS of complex organisms is tightly linked to understanding miRNA expression patterns. To facilitate these emerging studies, I here review the basic principles of medium- and high-throughput technologies available for miRNA expression profiling.

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Two Medfly Promoters That Have Originated by Recent Gene Duplication Drive Distinct Sex, Tissue and Temporal Expression Patterns

Genetics ◽

10.1093/genetics/156.1.173 ◽

2000 ◽

Vol 156 (1) ◽

pp. 173-182

Author(s):

George K Christophides ◽

Ioannis Livadaras ◽

Charalambos Savakis ◽

Katia Komitopoulou

Keyword(s):

Gene Expression ◽

Reporter Gene ◽

Fat Body ◽

Sequence Similarity ◽

Expression Patterns ◽

Gene Promoters ◽

Adult Males ◽

Specific Expression ◽

Cis Acting ◽

Genes Encoding

Abstract Genes encoding predominantly male-specific serum polypeptides (MSSPs) in the medfly Ceratitis capitata are members of a multigene family that are structurally similar to the genes encoding odorant binding proteins of insects. To study the transcriptional regulation of the genes MSSP-α2 and MSSP-β2, overlapping fragments of their promoters, containing the 5′ UTRs and 5′ flanking regions, were fused to the lacZ reporter gene and introduced into the medfly genome via Minos-mediated germline transformation. Transgenic flies were functionally assayed for β-galactosidase activity. Despite their extensive sequence similarity, the two gene promoters show distinct expression patterns of the reporter gene, consistent with previously reported evidence for analogous transcriptional activity of the corresponding endogenous genes. The MSSP-α2 promoter drives gene expression specifically in the fat body of the adult males, whereas the MSSP-β2 promoter directs gene expression in the midgut of both sexes. In contrast, similar transformation experiments in Drosophila melanogaster showed that both promoters drive the expression of the reporter gene in the midgut of adult flies of both sexes. Thus, the very same MSSP-α2 promoter fragment directs expression in the adult male fat body in Ceratitis, but in the midgut of both sexes in Drosophila. Our data suggest that through the evolution of the MSSP gene family a limited number of mutations that occurred within certain cis-acting elements, in combination with new medfly-specific trans-acting factors, endowed these recently duplicated genes with distinct sex-, tissue-, and temporal-specific expression patterns.

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PLncDB V2.0: a comprehensive encyclopedia of plant long noncoding RNAs

Nucleic Acids Research ◽

10.1093/nar/gkaa910 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D1489-D1495 ◽

Cited By ~ 1

Author(s):

Jingjing Jin ◽

Peng Lu ◽

Yalong Xu ◽

Zefeng Li ◽

Shizhou Yu ◽

...

Keyword(s):

Noncoding Rna ◽

Regulatory Networks ◽

Expression Patterns ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Data Driven ◽

Rna Seq ◽

Protein Coding ◽

User Friendly ◽

Coding Potential

Abstract Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with little or no protein coding potential. The expanding list of lncRNAs and accumulating evidence of their functions in plants have necessitated the creation of a comprehensive database for lncRNA research. However, currently available plant lncRNA databases have some deficiencies, including the lack of lncRNA data from some model plants, uneven annotation standards, a lack of visualization for expression patterns, and the absence of epigenetic information. To overcome these problems, we upgraded our Plant Long noncoding RNA Database (PLncDB, http://plncdb.tobaccodb.org/), which was based on a uniform annotation pipeline. PLncDB V2.0 currently contains 1 246 372 lncRNAs for 80 plant species based on 13 834 RNA-Seq datasets, integrating lncRNA information from four other resources including EVLncRNAs, RNAcentral and etc. Expression patterns and epigenetic signals can be visualized using multiple tools (JBrowse, eFP Browser and EPexplorer). Targets and regulatory networks for lncRNAs are also provided for function exploration. In addition, PLncDB V2.0 is hierarchical and user-friendly and has five built-in search engines. We believe PLncDB V2.0 is useful for the plant lncRNA community and data mining studies and provides a comprehensive resource for data-driven lncRNA research in plants.

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Elucidating another level of epigenetic regulation in osteoarthritis by identifying functional cis-acting long non-coding RNAs and their targets in articular cartilage

10.1101/2020.03.23.003020 ◽

2020 ◽

Author(s):

Marcella van Hoolwerff ◽

Paula I. Metselaar ◽

Margo Tuerlings ◽

H. Eka D. Suchiman ◽

Nico Lakenberg ◽

...

Keyword(s):

Regulatory Networks ◽

Differentially Expressed ◽

Sequencing Data ◽

Protein Coding ◽

Expression Levels ◽

Cis Acting ◽

Joint Replacement Surgery ◽

Replacement Surgery ◽

Antisense Lncrnas ◽

Non Coding Rnas

ABSTRACTObjectiveTo identify robustly differentially expressed long non-coding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage. Moreover to explore potential target mRNAs by establishing co-expression networks, followed by functional validation.MethodsRNA sequencing was performed on macroscopically lesioned and preserved OA cartilage of patients who underwent a joint replacement surgery due to OA (N=98). Differential expression (DE) analysis was performed on lncRNAs that were annotated in GENCODE and Ensembl. To identify potential interactions, correlations were calculated between the identified DE lncRNAs and previously reported DE protein-coding genes in the same samples. Modulation of chondrocyte lncRNA expression was achieved using LNA GapmeRs.ResultsBy applying our in-house pipeline we identified 5,053 lncRNAs to be robustly expressed, of which 191 were FDR significant differentially expressed between lesioned and preserved OA cartilage. Upon integrating mRNA sequencing data, we showed that intergenic and antisense DE lncRNAs show high, positive correlations with their flanking, respectively, sense genes. To functionally validate this observation we selected P3H2-AS1, which was downregulated in primary chondrocytes, resulting in downregulation of P3H2 gene expression levels. As such, we can confirm that P3H2-AS1 regulates its sense gene P3H2.ConclusionBy applying an improved detection strategy, robustly differentially expressed lncRNAs in OA cartilage were detected. Integration of these lncRNAs with differential mRNA expression levels in the same samples showed insight into their regulatory networks. Our data signifies that intergenic, as well as antisense lncRNAs play an important role in regulating the pathophysiology of OA.

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Identification and Characterization of Abiotic Stress Responsive CBL-CIPK Family Genes in Medicago

International Journal of Molecular Sciences ◽

10.3390/ijms22094634 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4634

Author(s):

Wenxuan Du ◽

Junfeng Yang ◽

Lin Ma ◽

Qian Su ◽

Yongzhen Pang

Keyword(s):

Abiotic Stress ◽

Abiotic Stresses ◽

Expression Patterns ◽

Interacting Protein ◽

Forage Crop ◽

Cis Acting ◽

Protein Motifs ◽

Plant Signal Transduction ◽

Identification And Characterization

The calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK) play important roles in plant signal transduction and response to abiotic stress. Plants of Medicago genus contain many important forages, and their growth is often affected by a variety of abiotic stresses. However, studies on the CBL and CIPK family member and their function are rare in Medicago. In this study, a total of 23 CBL and 58 CIPK genes were identified from the genome of Medicago sativa as an important forage crop, and Medicaog truncatula as the model plant. Phylogenetic analysis suggested that these CBL and CIPK genes could be classified into five and seven groups, respectively. Moreover, these genes/proteins showed diverse exon-intron organizations, architectures of conserved protein motifs. Many stress-related cis-acting elements were found in their promoter region. In addition, transcriptional analyses showed that these CBL and CIPK genes exhibited distinct expression patterns in various tissues, and in response to drought, salt, and abscisic acid treatments. In particular, the expression levels of MtCIPK2 (MsCIPK3), MtCIPK17 (MsCIPK11), and MtCIPK18 (MsCIPK12) were significantly increased under PEG, NaCl, and ABA treatments. Collectively, our study suggested that CBL and CIPK genes play crucial roles in response to various abiotic stresses in Medicago.

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Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-93531-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hibah Shaath ◽

Salman M. Toor ◽

Mohamed Abu Nada ◽

Eyad Elkord ◽

Nehad M. Alajez

Keyword(s):

Colorectal Cancer ◽

Messenger Rna ◽

Regulatory Networks ◽

Potential Interaction ◽

Therapeutic Interventions ◽

Signaling Networks ◽

Protein Coding ◽

Paired Samples ◽

And Migration ◽

Whole Transcriptome

AbstractColorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

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