Dynamic Expression and Regulatory Network of Circular RNA for Abdominal Preadipocytes Differentiation in Chicken (Gallus gallus)

Circular RNA (circRNA), as a novel endogenous biomolecule, has been emergingly demonstrated to play crucial roles in mammalian lipid metabolism and obesity. However, little is known about their genome-wide identification, expression profile, and function in chicken adipogenesis. In present study, the adipogenic differentiation of chicken abdominal preadipocyte was successfully induced, and the regulatory functional circRNAs in chicken adipogenesis were identified from abdominal adipocytes at different differentiation stages using Ribo-Zero RNA-seq. A total of 1,068 circRNA candidates were identified and mostly derived from exons. Of these, 111 differentially expressed circRNAs (DE-circRNAs) were detected, characterized by stage-specific expression, and enriched in several lipid-related pathways, such as Hippo signaling pathway, mTOR signaling pathway. Through weighted gene co-expression network analyses (WGCNA) and K-means clustering analyses, two DE-circRNAs, Z:35565770|35568133 and Z:54674624|54755962, were identified as candidate regulatory circRNAs in chicken adipogenic differentiation. Z:35565770|35568133 might compete splicing with its parental gene, ABHD17B, owing to its strictly negative co-expression. We also constructed competing endogenous RNA (ceRNA) network based on DE-circRNA, DE-miRNA, DE-mRNAs, revealing that Z:54674624|54755962 might function as a ceRNA to regulate chicken adipogenic differentiation through the gga-miR-1635-AHR2/IRF1/MGAT3/ABCA1/AADAC and/or the novel_miR_232-STAT5A axis. Translation activity analysis showed that Z:35565770|35568133 and Z:54674624|54755962 have no protein-coding potential. These findings provide valuable evidence for a better understanding of the specific functions and molecular mechanisms of circRNAs underlying avian adipogenesis.

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Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400882 ◽

2019 ◽

Vol 10 (1) ◽

pp. 235-246 ◽

Cited By ~ 3

Author(s):

Johanna Kurko ◽

Paul V. Debes ◽

Andrew H. House ◽

Tutku Aykanat ◽

Jaakko Erkinaro ◽

...

Keyword(s):

Atlantic Salmon ◽

Cell Fate ◽

Molecular Mechanisms ◽

Genome Wide Association Study ◽

Expression Patterns ◽

Hippo Signaling ◽

Age At Maturity ◽

Specific Expression ◽

Hpg Axis ◽

Tissue Specific

Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genes vgll3, akap11 and six6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns for vgll3, akap11 and six6. Correlated expression levels of vgll3 and akap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further, vgll3 correlating with arhgap6 and yap1, and akap11 with lats1 and yap1 suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate that vgll3 and akap11 paralogs have sex-dependent expression patterns in gonads. Moreover, six6 correlating with slc38a6 and rtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation.

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A tale of two cell-fates: role of the Hippo signaling pathway and transcription factors in early lineage formation in mouse preimplantation embryos

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa052 ◽

2020 ◽

Vol 26 (9) ◽

pp. 653-664

Author(s):

Challis Karasek ◽

Mohamed Ashry ◽

Chad S Driscoll ◽

Jason G Knott

Keyword(s):

Signaling Pathway ◽

Cell Fate ◽

Molecular Mechanisms ◽

Hippo Pathway ◽

Cell Mass ◽

Preimplantation Embryos ◽

Hippo Signaling ◽

Cell Fate Decisions ◽

Hippo Signaling Pathway ◽

The Hippo Pathway

Abstract In mammals, the first cell-fate decision occurs during preimplantation embryo development when the inner cell mass (ICM) and trophectoderm (TE) lineages are established. The ICM develops into the embryo proper, while the TE lineage forms the placenta. The underlying molecular mechanisms that govern lineage formation involve cell-to-cell interactions, cell polarization, cell signaling and transcriptional regulation. In this review, we will discuss the current understanding regarding the cellular and molecular events that regulate lineage formation in mouse preimplantation embryos with an emphasis on cell polarity and the Hippo signaling pathway. Moreover, we will provide an overview on some of the molecular tools that are used to manipulate the Hippo pathway and study cell-fate decisions in early embryos. Lastly, we will provide exciting future perspectives on transcriptional regulatory mechanisms that modulate the activity of the Hippo pathway in preimplantation embryos to ensure robust lineage segregation.

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LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway

Cell Death and Disease ◽

10.1038/s41419-020-03163-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jianheng Wu ◽

Nannan Wang ◽

Ying Yang ◽

Guangyuan Jiang ◽

Qingchun Mu ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Psychological Pain ◽

Protein Coding ◽

Proliferation And Apoptosis ◽

And Function

AbstractGlioblastoma multiforme (GBM) brings serious physical and psychological pain to GBM patients, whose survival rate remains not optimistic. Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of many cancers, including GBM. However, the mechanism and function of long intergenic non-protein coding RNA 1152 (LINC01152) in GBM are still unclear. In our study, we aimed to explore the function and mechanism of LINC01152 in GBM. Then qRT-PCR analysis was implemented to search the expression of RNAs in GBM tissues and cells. Functional assays such as EdU assay, colony formation assay, TUNEL assay and flow cytometry analysis were conducted to estimate GBM cell proliferation and apoptosis. RNA pull down assay, luciferase reporter assay, RIP and ChIP assays were implemented to search the binding between molecules. As a result, we discovered that LINC01152 was upregulated in GBM tissues and cells. LINC01152 and mastermind like transcriptional coactivator 2 (MAML2) could both play the oncogenic part in GBM. Moreover, LINC01152 positively regulated MAML2 in GBM by sponging miR-466 and recruiting SRSF1. In turn, RBPJ/MAML2 transcription complex was found to activate the transcription of LINC01152 in GBM cells. In conclusion, LINC01152 could upregulate the expression of MAML2 to promote tumorigenesis in GBM via Notch signaling pathway.

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Genome-wide expression and network analyses of mutants in key brassinosteroid signaling genes

BMC Genomics ◽

10.1186/s12864-021-07778-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Razgar Seyed Rahmani ◽

Tao Shi ◽

Dongzhi Zhang ◽

Xiaoping Gou ◽

Jing Yi ◽

...

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Differential Expression Analysis ◽

Transcriptional Level ◽

Partial Recovery ◽

Hormone Signaling ◽

Loss Of Function ◽

Altered Expression ◽

Network Analyses

Abstract Background Brassinosteroid (BR) signaling regulates plant growth and development in concert with other signaling pathways. Although many genes have been identified that play a role in BR signaling, the biological and functional consequences of disrupting those key BR genes still require detailed investigation. Results Here we performed phenotypic and transcriptomic comparisons of A. thaliana lines carrying a loss-of-function mutation in BRI1 gene, bri1–5, that exhibits a dwarf phenotype and its three activation-tag suppressor lines that were able to partially revert the bri1–5 mutant phenotype to a WS2 phenotype, namely bri1–5/bri1–1D, bri1–5/brs1–1D, and bri1–5/bak1–1D. From the three investigated bri1–5 suppressors, bri1–5/bak1–1D was the most effective suppressor at the transcriptional level. All three bri1–5 suppressors showed altered expression of the genes in the abscisic acid (ABA signaling) pathway, indicating that ABA likely contributes to the partial recovery of the wild-type phenotype in these bri1–5 suppressors. Network analysis revealed crosstalk between BR and other phytohormone signaling pathways, suggesting that interference with one hormone signaling pathway affects other hormone signaling pathways. In addition, differential expression analysis suggested the existence of a strong negative feedback from BR signaling on BR biosynthesis and also predicted that BRS1, rather than being directly involved in signaling, might be responsible for providing an optimal environment for the interaction between BRI1 and its ligand. Conclusions Our study provides insights into the molecular mechanisms and functions of key brassinosteroid (BR) signaling genes, especially BRS1.

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Genome-Wide Expression and Network Analyses of Mutants in Key Brassinosteroid Signaling Genes

10.21203/rs.3.rs-75547/v1 ◽

2020 ◽

Author(s):

Razgar Seyed Rahmani ◽

Tao Shi ◽

Dongzhi Zhang ◽

Xiaoping Gou ◽

Jing Yi ◽

...

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Differential Expression Analysis ◽

Transcriptional Level ◽

Partial Recovery ◽

Hormone Signaling ◽

Loss Of Function ◽

Altered Expression ◽

Network Analyses

Abstract BackgroundBrassinosteroid (BR) signaling regulates plant growth and development in concert with other signaling pathways. Although many genes have been identified that play a role in Brassinosteroid (BR) signaling, the biological and functional consequences of disrupting those key BR genes still requires detailed investigation.ResultsHere we performed phenotypic and transcriptomic comparisons of A. thaliana lines carrying a loss-of-function mutation in BRI1 gene, bri1-5, that exhibits a dwarf phenotype along with its three activation-tag suppressor lines that were able to partially revert the bri1-5 mutant phenotype to a WT phenotype, namely bri1-5/bri1-1D, bri1-5/brs1-1D, bri1-5/bak1-1D. From the three investigated bri1-5 suppressors, bri1-5/bak1-1D was the most effective suppressor at the transcriptional level. All three bri1-5 suppressors showed altered expression of the genes in the abscisic acid (ABA signaling) pathway, indicating that ABA likely contributes to the partial recovery of the wild type phenotype in these bri1-5 suppressors. Network analysis revealed crosstalk between BR and other phytohormone signaling pathways, suggesting that interference with one hormone signaling pathway affects other hormone signaling pathways. In addition, differential expression analysis suggested the existence of a strong negative feedback from BR signaling on BR biosynthesis and also predicted that BRS1, rather than being directly involved in signaling, is likely responsible for providing an optimal environment for the interaction between BRI1 and its ligand. ConclusionsOur study provides insights into the molecular mechanisms and functions of key brassinosteroid (BR) signaling genes, especially BRS1.

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RASSF1A-Mediated Suppression of Estrogen Receptor Alpha (ERα)-Driven Breast Cancer Cell Growth Depends on the Hippo-Kinases LATS1 and 2

Cells ◽

10.3390/cells10112868 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2868

Author(s):

Sven Roßwag ◽

Jonathan P. Sleeman ◽

Sonja Thaler

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Tumor Suppressor ◽

Estrogen Receptor Alpha ◽

Molecular Mechanisms ◽

Hippo Pathway ◽

Hippo Signaling ◽

Breast Cancers ◽

Receptor Alpha ◽

And Function

Around 70% of breast cancers express the estrogen receptor alpha (ERα). This receptor is of central importance for breast cancer development and estrogen-dependent tumor growth. However, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast carcinogenesis are complex and not fully understood. In previous work, we have demonstrated that the tumor suppressor RASSF1A suppresses estrogen-dependent growth of breast cancer cells through a complex network that keeps ERα expression and function under control. We observed that RASSF1A mediates the suppression of ERα expression through modulation of the Hippo effector Yes-associated protein 1 (YAP1) activity. Here we report that RASSF1A-mediated alteration of YAP1 depends on the Hippo-kinases LATS1 and LATS2. Based on these results, we conclude that inactivation of RASSF1A causes changes in the function of the Hippo signaling pathway and altered activation of YAP1, and as a consequence, increased expression and function of ERα. Thus, the inactivation of RASSF1A might constitute a fundamental event that supports the initiation of ERα-dependent breast cancer. Furthermore, our results support the notion that the Hippo pathway is important for the suppression of luminal breast cancers, and that the tumor-suppressor function of RASSF1A depends on LATS1 and LATS2.

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Evolutionarily conserved transcriptional landscape of the heart defining the chamber specific physiology

10.1101/2021.01.22.427752 ◽

2021 ◽

Author(s):

Shrey Gandhi ◽

Anika Witten ◽

Federica deMajo ◽

Martijn Gilbers ◽

Jos Maessen ◽

...

Keyword(s):

Molecular Mechanisms ◽

Expression Patterns ◽

Circular Rna ◽

Model Organisms ◽

Protein Coding ◽

Evolutionarily Conserved ◽

Cardiovascular Biology ◽

Novel Therapeutic Strategies ◽

Transcriptional Landscape

AbstractCardiovascular disease (CVD) remains the leading cause of death worldwide. A deeper characterization of the regional transcription patterns within different heart chambers may aid to improve our understanding of the molecular mechanisms involved in the function of the heart as well as our ability to develop novel therapeutic strategies. Here, we determined differentially expressed protein coding, long non-coding (lncRNA) and circular RNA (CircRNA) genes within various heart chambers across seven vertebrate species. We identified chamber specific genes, lncRNAs and pathways that are evolutionarily conserved in vertebrates. Further, we identified lncRNA homologs based on sequence, secondary structure, synteny and expressional conservation. Interestingly, most lncRNAs were found to be syntenically conserved. Various factors affect the co-expression patterns of transcripts including (i) genomic overlap, (ii) strandedness and (iii) transcript biotype. We also provide a catalogue of CircRNAs which are abundantly expressed across vertebrate hearts. Finally, we established a repository called EvoACTG (http://evoactg.uni-muenster.de/), which provides information about the conserved expression patterns for both PC genes and non-coding RNAs (ncRNAs) in the various heart chambers, and may serve as a community resource for investigators interested in the (patho)-physiology of CVD. We believe that this study will inform researchers working in the field of cardiovascular biology to explore the conserved yet intertwined nature of both coding and non-coding cardiac transcriptome across various popular model organisms in CVD research.

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The Hippo Signaling Pathway in the Regulation of Skeletal Muscle Mass and Function

Exercise and Sport Sciences Reviews ◽

10.1249/jes.0000000000000142 ◽

2018 ◽

Vol 46 (2) ◽

pp. 92-96 ◽

Cited By ~ 8

Author(s):

Kevin I. Watt ◽

Craig A. Goodman ◽

Troy A. Hornberger ◽

Paul Gregorevic

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

And Function

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Closing the circle: current state and perspectives of circular RNA databases

Briefings in Bioinformatics ◽

10.1093/bib/bbz175 ◽

2020 ◽

Cited By ~ 5

Author(s):

Marieke Vromman ◽

Jo Vandesompele ◽

Pieter-Jan Volders

Keyword(s):

Splice Junction ◽

Circular Rna ◽

Circular Rnas ◽

Working Mechanism ◽

Comprehensive Overview ◽

Specific Expression ◽

Protein Coding ◽

Rna Molecules ◽

Current State ◽

Coding Potential

Abstract Circular RNAs (circRNAs) are covalently closed RNA molecules that have been linked to various diseases, including cancer. However, a precise function and working mechanism are lacking for the larger majority. Following many different experimental and computational approaches to identify circRNAs, multiple circRNA databases were developed as well. Unfortunately, there are several major issues with the current circRNA databases, which substantially hamper progression in the field. First, as the overlap in content is limited, a true reference set of circRNAs is lacking. This results from the low abundance and highly specific expression of circRNAs, and varying sequencing methods, data-analysis pipelines, and circRNA detection tools. A second major issue is the use of ambiguous nomenclature. Thus, redundant or even conflicting names for circRNAs across different databases contribute to the reproducibility crisis. Third, circRNA databases, in essence, rely on the position of the circRNA back-splice junction, whereas alternative splicing could result in circRNAs with different length and sequence. To uniquely identify a circRNA molecule, the full circular sequence is required. Fourth, circRNA databases annotate circRNAs’ microRNA binding and protein-coding potential, but these annotations are generally based on presumed circRNA sequences. Finally, several databases are not regularly updated, contain incomplete data or suffer from connectivity issues. In this review, we present a comprehensive overview of the current circRNA databases and their content, features, and usability. In addition to discussing the current issues regarding circRNA databases, we come with important suggestions to streamline further research in this growing field.

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The calcium channel subunit α2δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway

Nature Communications ◽

10.1038/s41467-019-13165-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Kendall M. Hoover ◽

Scott J. Gratz ◽

Nova Qi ◽

Kelsey A. Herrmann ◽

Yizhou Liu ◽

...

Keyword(s):

Growth Factor ◽

Calcium Channel ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Structure And Function ◽

Bmp Signaling ◽

Growth Factor Signaling ◽

Activity State ◽

And Function ◽

Activity Dependent

AbstractSynapses are highly specialized for neurotransmitter signaling, yet activity-dependent growth factor release also plays critical roles at synapses. While efficient neurotransmitter signaling relies on precise apposition of release sites and neurotransmitter receptors, molecular mechanisms enabling high-fidelity growth factor signaling within the synaptic microenvironment remain obscure. Here we show that the auxiliary calcium channel subunit α2δ-3 promotes the function of an activity-dependent autocrine Bone Morphogenetic Protein (BMP) signaling pathway at the Drosophila neuromuscular junction (NMJ). α2δ proteins have conserved synaptogenic activity, although how they execute this function has remained elusive. We find that α2δ-3 provides an extracellular scaffold for an autocrine BMP signal, suggesting a mechanistic framework for understanding α2δ’s conserved role in synapse organization. We further establish a transcriptional requirement for activity-dependent, autocrine BMP signaling in determining synapse density, structure, and function. We propose that activity-dependent, autocrine signals provide neurons with continuous feedback on their activity state for modulating both synapse structure and function.

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