Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Sci Total Environ
2020 Mar 20;709:136045. doi: 10.1016/j.scitotenv.2019.136045.
Show Gene links
Show Anatomy links
The regulation mechanism of lncRNAs and mRNAs in sea cucumbers under global climate changes: Defense against thermal and hypoxic stresses.
Huo D
,
Sun L
,
Storey KB
,
Zhang L
,
Liu S
,
Sun J
,
Yang H
.
???displayArticle.abstract???
The aquatic environment can be greatly impacted by thermal and hypoxic stresses, particularly caused by intensified global warming. Hence, there is an urgency to understand the response mechanisms of marine organisms to adverse environment. Although long non-coding RNAs (lncRNAs) are involved in many biological processes, their roles in stress responses still remain unclear. Here, differentially expressed (DE) lncRNAs and mRNAs were identified as responses to environmental stresses in the economically important sea cucumber, Apostichopus japonicus, and their potential roles were explored. Based on a total of 159, 355 and 495 significantly upregulated genes and 230, 518 and 647 significantly downregulated genes identified in the thermal, hypoxic and combination thermal + hypoxic stress treatments, respectively, we constructed DE-lncRNA-mRNA coexpression networks. Among the networks, eight shared pairs were identified from the three treatments, and based on the connectivity degree, MSTRG.27265, MSTRG.19729 and MSTRG.95524 were shown to be crucial lncRNAs. Among all the significantly changed lncRNAs identified by RT-qPCR and sequencing data, binding sites were found in four other lncRNAs (MSTRG.34610, MSTRG.10941, MSTRG.81281 and MSTRG.93731) with Aja-miR-2013-3p, a key miRNA that responds to hypoxia in sea cucumbers. The hypoxia-inducible factor (HIF-1α) was also shown as the possible targeted mRNA of Aja-miR-2013-3p. As indicated by a dual-luciferase reporter assay system, "HIF-1α gene/Aja-miR-2013-3p/MSTRG.34610" network and the "HIF-1α gene/Aja-miR-2013-3p/MSTRG.10941" network may play important roles in sea cucumbers under environmental stresses. Moreover, environmental stress altered the expression of multiple lncRNAs and mRNAs, thus affecting various biological processes in A. japonicus, including immunity, energy metabolism and the cell cycle. At the molecular level, more comprehensive responses were elicited by the combined thermal/hypoxic stress treatment than by individual stresses alone in sea cucumbers. This study lays the groundwork for future research on molecular mechanisms of echinoderm responses to thermal and hypoxic stress in the context of global climate changes.
Fig. 1. Characteristic of identified lncRNAs vs mRNAs in the sea cucumber.
Fig. 2. Validation of high throughput sequencing results using RT-qPCR.
Fig. 3. Gene ontology analysis of differentially expressed mRNAs and lncRNAs.
Fig. 4. LncRNA-mRNA interactive network for comparison of (a) HT vs. NC; (b) LO vs. NC; (c) HL vs. NC and (d) 8 co-identified DE lncRNA-mRNA pairs. Up-regulated mRNAs are displayed as red squares, down-regulated mRNAs are displayed as blue squares. Up-regulated lncRNAs are displayed as red triangles, and down-regulated lncRNAs are displayed as blue triangles. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5. Dual-luciferase assay reporter system results of mRNA-miRNA (mmi) and lncRNA and miRNA (lmi). (mmi2: 3ⲠUTR-NC + miRNA; mmi4: 3ⲠUTR + miRNA; lmi2: 3ⲠUTR-NC + miRNA; lmi4: MSTRG10941.1(Aja-miR-2013-3p) + miRNA; lmi6: MSTRG10941.1(Aja-miR-2013-3p)-mut + miRNA; lmi8: MSTRG81281.1(Aja-miR-2013-3p) + miRNA; lmi12: MSTRG93731.1(Aja-miR-2013-3p) + miRNA; lmi16: MSTRG34610.1(Aja-miR-2013-3p) + miRNA; PC-miRNA NC: 3ⲠUTR positive control + miRNA-NC; PC-miRNA: 3ⲠUTR positive control + miRNA positive control; * p < 0.05, ** p < 0.01, *** p < 0.001).
Fig. 6. Key lncRNA-miRNA-mRNA networks in sea cucumbers under environmental stress. (a) network diagram; (b) sequence information (seed region was shown in red, complementary pairings were shown in yellow grounding); (c) predicted binding structure of Aja-miR-2013-3p and the mature Aja-miR-2013-3p sequence (shown in capital letter). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. S1. Venn diagram of identified lncRNAs.
Fig. S2. Hierarchical clustering of (a) lncRNAs and (b) mRNAs in stress-treated individuals and healthy controls. HT1-HT3: sea cucumbers under high temperature treatment; LO1-LO3: sea cucumbers under low dissolved oxygen treatment; HL1-HL3: sea cucumbers under high temperature and low dissolved oxygen treatment; NC1-NC3: healthy sea cucumbers under normal conditions.
Fig. S3. Volcano plot of DE-mRNA and DE-lncRNA.
Fig. S4. Relative expression of lncRNAs, miRNAs and mRNAs used for DLRAS.
Alzan,
Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.
2016, Pubmed
Alzan,
Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi.
2016,
Pubmed
Baze,
Chronic hypoxia stimulates an enhanced response to immune challenge without evidence of an energetic tradeoff.
2011,
Pubmed
Carrieri,
Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat.
2012,
Pubmed
Chen,
Gene regulation in the immune system by long noncoding RNAs.
2017,
Pubmed
Devaux,
Long noncoding RNAs in cardiac development and ageing.
2015,
Pubmed
Fatica,
Long non-coding RNAs: new players in cell differentiation and development.
2014,
Pubmed
Feng,
Transcriptional profiling of long non-coding RNAs in mantle of Crassostrea gigas and their association with shell pigmentation.
2018,
Pubmed
Gonzalez,
A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature.
2015,
Pubmed
Gupta,
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.
2010,
Pubmed
Han,
LncRNA profile of glioblastoma reveals the potential role of lncRNAs in contributing to glioblastoma pathogenesis.
2012,
Pubmed
Heward,
Long non-coding RNAs in the regulation of the immune response.
2014,
Pubmed
Huo,
Global-warming-caused changes of temperature and oxygen alter the proteomic profile of sea cucumber Apostichopus japonicus.
2019,
Pubmed
,
Echinobase
Huo,
Differential Expression of miRNAs in the Respiratory Tree of the Sea Cucumber Apostichopus japonicus Under Hypoxia Stress.
2017,
Pubmed
,
Echinobase
Huo,
Impact of hypoxia stress on the physiological responses of sea cucumber Apostichopus japonicus: respiration, digestion, immunity and oxidative damage.
2018,
Pubmed
,
Echinobase
Huo,
Metabolome responses of the sea cucumber Apostichopus japonicus to multiple environmental stresses: Heat and hypoxia.
2019,
Pubmed
,
Echinobase
Ibeagha-Awemu,
Integration of lncRNA and mRNA Transcriptome Analyses Reveals Genes and Pathways Potentially Involved in Calf Intestinal Growth and Development during the Early Weeks of Life.
2018,
Pubmed
Jin,
Chronic heat stress weakened the innate immunity and increased the virulence of highly pathogenic avian influenza virus H5N1 in mice.
2011,
Pubmed
Kowalczyk,
Molecular biology: RNA discrimination.
2012,
Pubmed
Li,
Identification of long non-protein coding RNAs in chicken skeletal muscle using next generation sequencing.
2012,
Pubmed
Li,
Identification of circRNAs for miRNA Targets by Argonaute2 RNA Immunoprecipitation and Luciferase Screening Assays.
2018,
Pubmed
Liu,
Genome-wide analysis uncovers regulation of long intergenic noncoding RNAs in Arabidopsis.
2012,
Pubmed
Lowe,
Expression of rat intestinal fatty acid-binding protein in Escherichia coli. Purification and comparison of ligand binding characteristics with that of Escherichia coli-derived rat liver fatty acid-binding protein.
1987,
Pubmed
Mastellos,
Complement: more than a 'guard' against invading pathogens?
2002,
Pubmed
Mercer,
Structure and function of long noncoding RNAs in epigenetic regulation.
2013,
Pubmed
Nakanishi,
The effect of polymorphism in the intestinal fatty acid-binding protein 2 gene on fat metabolism is associated with gender and obesity amongst non-diabetic Japanese-Americans.
2004,
Pubmed
Nam,
Long noncoding RNAs in C. elegans.
2012,
Pubmed
Nelson,
The translation machinery and 70 kd heat shock protein cooperate in protein synthesis.
1992,
Pubmed
Nguyen,
Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts.
2012,
Pubmed
Nyberg,
Comparative Expression Dynamics of Intergenic Long Noncoding RNAs in the Genus Drosophila.
2016,
Pubmed
Park,
MicroRNA-146a and microRNA-146b regulate human dendritic cell apoptosis and cytokine production by targeting TRAF6 and IRAK1 proteins.
2015,
Pubmed
Pauli,
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis.
2012,
Pubmed
Rehmsmeier,
Fast and effective prediction of microRNA/target duplexes.
2004,
Pubmed
Roberts,
Heat shock proteins (chaperones) in fish and shellfish and their potential role in relation to fish health: a review.
2010,
Pubmed
Salmena,
A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?
2011,
Pubmed
Schmittgen,
Analyzing real-time PCR data by the comparative C(T) method.
2008,
Pubmed
Shannon,
Cytoscape: a software environment for integrated models of biomolecular interaction networks.
2003,
Pubmed
Shukla,
The role of microRNAs and other endogenous small RNAs in plant stress responses.
2008,
Pubmed
Sipiläinen,
Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects.
1997,
Pubmed
Valenzuela-Miranda,
Novel insights into the response of Atlantic salmon (Salmo salar) to Piscirickettsia salmonis: Interplay of coding genes and lncRNAs during bacterial infection.
2016,
Pubmed
Wang,
Characteristics of long non-coding RNAs in the Brown Norway rat and alterations in the Dahl salt-sensitive rat.
2014,
Pubmed
Wang,
Analyses of Long Non-Coding RNA and mRNA profiling using RNA sequencing during the pre-implantation phases in pig endometrium.
2016,
Pubmed
Wapinski,
Long noncoding RNAs and human disease.
2011,
Pubmed
Yang,
Expression of immune-related genes in embryos and larvae of sea cucumber Apostichopus japonicus.
2010,
Pubmed
,
Echinobase
Yoon,
LincRNA-p21 suppresses target mRNA translation.
2012,
Pubmed
Yoon,
Posttranscriptional gene regulation by long noncoding RNA.
2013,
Pubmed
Zhang,
The sea cucumber genome provides insights into morphological evolution and visceral regeneration.
2017,
Pubmed
,
Echinobase