Miniature inverted repeat transposable elements (MITEs) cis-regulate circular RNA expression and promote ethylene biosynthesis, reducing poplar heat tolerance

2020 ◽  
Author(s):  
Yuepeng Song ◽  
Chenhao Bu ◽  
Panfei Chen ◽  
Peng Liu ◽  
Deqiang Zhang
Keyword(s):  
Transposable Elements ◽  
Heat Tolerance ◽  
Protein Modification ◽  
Membrane Lipids ◽  
Circular Rna ◽  
Ethylene Biosynthesis ◽  
Negative Regulator ◽  
Circular Rnas ◽  
Nucleotide Polymorphisms ◽  
Complementary Sequence

Abstract Transposable elements (TEs) and their reverse complementary sequence pairs (RCPs) are enriched around loci that produce circular RNAs (circRNAs) in plants. However, the function of these TE–RCP pairs in modulating circRNA expression remains elusive. Here, we identified 4,609 circRNAs in poplar (Populus tomentosa) and showed that MITEs-RCPs were enriched in circRNA flanking regions. Moreover, we used expression quantitative trait nucleotide (eQTN) mapping to decipher the cis-regulatory role of MITEs. eQTN results showed that fourteen single-nucleotide polymorphisms (SNPs) were significantly associated with Circ_0000408 and Circ_0003418 levels and the lead associated SNPs were located in MITE–RCP regions, indicating that MITE-RCP sequence variations affect exon circularization. Overexpression and knockdown analysis showed that Circ_0003418 positively modulated its parental gene, which encodes the RING-type E3 ligase XBAT32, and specifically increased the expression of the PtoXBAT32.5 transcript variant, which lacks the E3 ubiquitin ligase domain. Under heat stress, PtoXBAT32.5 expression was induced with upregulation of Circ_0003418, resulting in increased production of ethylene and peroxidation of membrane lipids. Our findings thus reveal the cis-regulatory mechanism by which a MITE–RCP pair affects circRNA abundance in poplar and indicate that Circ_0003418 is a negative regulator of poplar heat tolerance via the ubiquitin-mediated protein modification pathway.

scholarly journals Circular RNA repertoires are associated with evolutionarily young transposable elements

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Franziska Gruhl ◽  
Peggy Janich ◽  
Henrik Kaessmann ◽  
David Gatfield
Keyword(s):  
Transposable Elements ◽  
Repetitive Sequences ◽  
Purifying Selection ◽  
Circular Rna ◽  
Circular Rnas ◽  
Orthologous Genes ◽  
Transposon Insertion ◽  
Orthologous Loci ◽  
Transcriptional Gene Regulation ◽  
Species Specific

Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.

scholarly journals Circular RNA repertoires are associated with evolutionarily young transposable elements

2021 ◽  
Author(s):  
Franziska Gruhl ◽  
Peggy Janich ◽  
Henrik Kaessmann ◽  
David Gatfield
Keyword(s):  
Transposable Elements ◽  
Repetitive Sequences ◽  
Purifying Selection ◽  
Circular Rna ◽  
Circular Rnas ◽  
Transposable Element Insertion ◽  
Orthologous Genes ◽  
Orthologous Loci ◽  
Transcriptional Gene Regulation ◽  
Species Specific

AbstractCircular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires across five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across different species. Even the circRNAs from the orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution – as a byproduct of splicing in orthologs prone to transposable element insertion. Overall, our findings argue against widespread functional circRNA conservation.

scholarly journals Comprehensive profiling analysis of the N6-methyladenosine-modified circular RNA transcriptome in cultured cells infected with Marek’s disease virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aijun Sun ◽  
Rui Wang ◽  
Shuaikang Yang ◽  
Xiaojing Zhu ◽  
Ying Liu ◽  
...  
Keyword(s):  
Disease Virus ◽  
Cultured Cells ◽  
Circular Rna ◽  
Marek's Disease Virus ◽  
Marek's Disease ◽  
Circular Rnas ◽  
Marek’S Disease Virus ◽  
Marek’S Disease ◽  
Pathway Analyses ◽  
Profiling Analysis

AbstractMarek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

scholarly journals Correlation of Circular RNA hsa_circ_0001946, hsa_circ_0125589, and Environmental Factors With Hypertension

2020 ◽  
Vol 33 (11) ◽  
pp. 1047-1047
Author(s):  
Wan-yue Liu ◽  
Yi Sun ◽  
Shu-na Huang ◽  
Yu-zhen Lin ◽  
Hong-yan Guo ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Peripheral Blood ◽  
Circular Rna ◽  
Peripheral Blood Lymphocytes ◽  
Normal Weight ◽  
Circular Rnas ◽  
Blood Leukocytes ◽  
Crossover Analysis ◽  
History Of ◽  
The Relationship

Abstract Background To investigate the main environmental factors of hypertension and the relationship between hypertension and circular RNAs in peripheral blood lymphocytes. Methods This was a case–control study. A total of 681 hypertension patients and 485 subjects without hypertension were recruited between April 2017 and October 2018. All participations completed the questionnaire investigation, physical examination, and laboratory detection. Quantitative real-time polymerase chain reaction was used to analyze circRNAs (hsa_circ_0001946 and hsa_circ_0125589) in peripheral blood leukocytes in 84 hypertensives and 84 controls. Multivariate logistic regression and crossover analysis were used to analyze the interaction and association between environmental factors and circRNAs in hypertension. Results After adjusted by gender, age and marital status, overweight/obesity (odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.24–2.22), abdominal obesity (OR = 2.17, 95% CI 1.54–3.04), anxiety (OR = 2.15, 95% CI 1.41–3.28), family history of hypertension (OR = 4.26, 95% CI 3.18–5.70), and higher levels of hsa_circ_0001946 (OR = 4.13, 95% CI 1.85–9.21) were risk factors for hypertension, while levels of hsa_circ_0125589 were not associated with hypertension. Crossover analysis showed that the risk of hypertension was 13.12 times higher (95% CI 3.89–44.23) in overweight subjects with high hsa_circ_0001946 levels compared with normal weight subjects with low hsa_circ_0001946 levels. Further, the risk of hypertension was 17.78 times higher (95% CI 1.88–168.61) in subjects with anxiety and high hsa_circ_0001946 levels. Conclusions Hypertension is the result of both environmental factors and genetic factors. Higher hsa_circ_0001946 levels, overweight and anxiety may increase the risk of hypertension, while hsa_circ_0125589 levels are not related to hypertension.

scholarly journals Stablization of ACOs by NatB mediated N-terminal acetylation is required for ethylene homeostasis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hai-qing Liu ◽  
Ya-jie Zou ◽  
Xiao-feng Li ◽  
Lei Wu ◽  
Guang-qin Guo
Keyword(s):  
Protein Modification ◽  
Normal Growth ◽  
Ethylene Biosynthesis ◽  
Regulation Mechanism ◽  
Biological Functions ◽  
Loss Of Function ◽  
Auxiliary Subunit ◽  
Ethylene Content ◽  
Endogenous Ethylene ◽  
Exogenous Ethylene

AbstractN-terminal acetylation (NTA) is a highly abundant protein modification catalyzed by N-terminal acetyltransferases (NATs) in eukaryotes. However, the plant NATs and their biological functions have been poorly explored. Here we reveal that loss of function of CKRC3 and NBC-1, the auxiliary subunit (Naa25) and catalytic subunit (Naa20) of Arabidopsis NatB, respectively, led to defects in skotomorphogenesis and triple responses of ethylene. Proteome profiling and WB test revealed that the 1-amincyclopropane-1-carboxylate oxidase (ACO, catalyzing the last step of ethylene biosynthesis pathway) activity was significantly down-regulated in natb mutants, leading to reduced endogenous ethylene content. The defective phenotypes could be fully rescued by application of exogenous ethylene, but less by its precursor ACC. The present results reveal a previously unknown regulation mechanism at the co-translational protein level for ethylene homeostasis, in which the NatB-mediated NTA of ACOs render them an intracellular stability to maintain ethylene homeostasis for normal growth and responses.

scholarly journals The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cyclin E1 ◽  
Normal Tissues ◽  
Exact Function ◽  
Potential Biomarker

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Results Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

scholarly journals Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xuexiu Zhang ◽  
Jianning Yao ◽  
Haoling Shi ◽  
Bing Gao ◽  
Haining Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Sp1 Transcription Factor ◽  
Reporter Assays ◽  
Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

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