scholarly journals Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis

2018 ◽  
Author(s):  
Hemakumar M Reddy ◽  
Rupa Bhattacharya ◽  
Zeenath Jehan ◽  
Kankadeb Mishra ◽  
Pranatharthi Annapurna ◽  
...  
Keyword(s):  
Male Fertility ◽  
Noncoding Rna ◽  
Splice Variants ◽  
Noncoding Rnas ◽  
Autosomal Gene ◽  
Male Sterile ◽  
Transcript Variants ◽  
Sperm Abnormalities ◽  
Sterile Hybrids

Majority of the genes expressed during spermatogenesis are autosomal. Mice with different deletions of Yq show sub-fertility, sterility and sperm abnormalities. The connection between Yq deletion and autosomal gene regulation is not well understood. We describe a novel mouse Yq-derived long noncoding RNA, Pirmy, which shows unprecedented number of splice variants in testis. Further, Pirmy transcript variants act as templates for several piRNAs. We identified ten differentially expressed autosome-encoded sperm proteins in mutant mice. Pirmy transcript variants have homology to &5acute/&3acuteUTRs of these deregulated autosomal genes. Thus, subfertility in Y-deleted mice appears to be a polygenic phenomenon that is partially regulated epistatically by the Y-chromosome. Our study provides novel insights into possible role of MSY-derived ncRNAs in male fertility and reproduction. Finally, sperm phenotypes from the Y-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of Y-derived ncRNAs in male sterility and speciation.

scholarly journals Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hemakumar M. Reddy ◽  
Rupa Bhattacharya ◽  
Shrish Tiwari ◽  
Kankadeb Mishra ◽  
Pranatharthi Annapurna ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Splice Variants ◽  
Noncoding Rnas ◽  
Mouse Testis ◽  
Autosomal Gene ◽  
Male Sterile ◽  
Multiple Copies ◽  
Male Specific

Abstract Background Deciphering the functions of Y chromosome in mammals has been slow owing to the presence of repeats. Some of these repeats transcribe coding RNAs, the roles of which have been studied. Functions of the noncoding transcripts from Y chromosomal repeats however, remain unclear. While a majority of the genes expressed during spermatogenesis are autosomal, mice with different deletions of the long arm of the Y chromosome (Yq) were previously also shown to be characterized by subfertility, sterility and sperm abnormalities, suggesting the presence of effectors of spermatogenesis at this location. Here we report a set of novel noncoding RNAs from mouse Yq and explore their connection to some of the autosomal genes expressed in testis. Results We describe a set of novel mouse male-specific Y long arm (MSYq)-derived long noncoding (lnc) transcripts, named Pirmy and Pirmy-like RNAs. Pirmy shows a large number of splice variants in testis. We also identified Pirmy-like RNAs present in multiple copies at different loci on mouse Y chromosome. Further, we identified eight differentially expressed autosome-encoded sperm proteins in a mutant mouse strain, XYRIIIqdel (2/3 Yq-deleted). Pirmy and Pirmy-like RNAs have homology to 5′/3′UTRs of these deregulated autosomal genes. Several lines of experiments show that these short homologous stretches correspond to piRNAs. Thus, Pirmy and Pirmy-like RNAs act as templates for several piRNAs. In vitro functional assays reveal putative roles for these piRNAs in regulating autosomal genes. Conclusions Our study elucidates a set of autosomal genes that are potentially regulated by MSYq-derived piRNAs in mouse testis. Sperm phenotypes from the Yq-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of MSYq-derived ncRNAs in male sterility and speciation.

scholarly journals Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

2019 ◽  
Vol 20 (8) ◽  
pp. 1924 ◽  
Author(s):  
Gugnoni ◽  
Ciarrocchi
Keyword(s):  
Cancer Biology ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Protein Localization ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Mesenchymal Transition ◽  
Multistep Process ◽  
Genomic Studies

Epithelial–mesenchymal transition (EMT) is a multistep process that allows epithelial cells to acquire mesenchymal properties. Fundamental in the early stages of embryonic development, this process is aberrantly activated in aggressive cancerous cells to gain motility and invasion capacity, thus promoting metastatic phenotypes. For this reason, EMT is a central topic in cancer research and its regulation by a plethora of mechanisms has been reported. Recently, genomic sequencing and functional genomic studies deepened our knowledge on the fundamental regulatory role of noncoding DNA. A large part of the genome is transcribed in an impressive number of noncoding RNAs. Among these, long noncoding RNAs (lncRNAs) have been reported to control several biological processes affecting gene expression at multiple levels from transcription to protein localization and stability. Up to now, more than 8000 lncRNAs were discovered as selectively expressed in cancer cells. Their elevated number and high expression specificity candidate these molecules as a valuable source of biomarkers and potential therapeutic targets. Rising evidence currently highlights a relevant function of lncRNAs on EMT regulation defining a new layer of involvement of these molecules in cancer biology. In this review we aim to summarize the findings on the role of lncRNAs on EMT regulation and to discuss their prospective potential value as biomarkers and therapeutic targets in cancer.

scholarly journals Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1

2020 ◽  
Vol 48 (8) ◽  
pp. 4480-4491 ◽  
Author(s):  
Xiaoyan Wang ◽  
Xinyue Zhang ◽  
Yujie Dang ◽  
Duan Li ◽  
Gang Lu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Noncoding Rna ◽  
Dna Damage Repair ◽  
Noncoding Rnas ◽  
Epigenetic Mechanism ◽  
Premature Ovarian Insufficiency ◽  
Genetic Etiology ◽  
Ovarian Insufficiency ◽  
Damage Repair

Abstract The genetic etiology of premature ovarian insufficiency (POI) has been well established to date, however, the role of long noncoding RNAs (lncRNAs) in POI is largely unknown. In this study, we identified a down-expressed lncRNA HCP5 in granulosa cells (GCs) from biochemical POI (bPOI) patients, which impaired DNA damage repair and promoted apoptosis of GCs. Mechanistically, we discovered that HCP5 stabilized the interaction between YB1 and its partner ILF2, which could mediate YB1 transferring into the nucleus of GCs. HCP5 silencing affected the localization of YB1 into nucleus and reduced the binding of YB1 to the promoter of MSH5 gene, thereby diminishing MSH5 expression. Taken together, we identified that the decreased expression of HCP5 in bPOI contributed to dysfunctional GCs by regulating MSH5 transcription and DNA damage repair via the interaction with YB1, providing a novel epigenetic mechanism for POI pathogenesis.

scholarly journals Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Comprehensive Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

264The long noncoding RNA H19 modulates cardiac remodeling after infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O K Choong ◽  
C Y Chen ◽  
J H Lin ◽  
P J Lin ◽  
J H Zhang ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Noncoding Rna ◽  
Cardiac Fibrosis ◽  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Noncoding Rnas ◽  
Interacting Protein ◽  
Functional Studies ◽  
Rna Purification

Abstract Noncoding RNAs account for 80% of human transcripts, but functional studies on noncoding RNAs are relatively few and limited. Long noncoding RNAs (lncRNAs) are known to have an important role in cardiac development, and lately, high-throughput RNA sequencing has been extensively utilized to profile and explore the transcriptome landscape of lncRNAs in failing hearts. These studies have revealed that lncRNAs are mostly dysregulated in failing hearts and their expression signature can discriminate failing hearts of different etiologies. H19 is abundantly expressed in failing human hearts and its polymorphism was shown to possess a significant correlation with the risk of coronary artery diseases. In our study using murine hearts, we discovered that H19 was significantly up regulated in the heart after ischemic injury, with predominant expression in cardiac fibroblasts. This finding piqued our interest to further investigate the function of H19 in the heart. We demonstrated that ectopic overexpression of H19 using the AAV approach led to severe cardiac fibrosis in mouse hearts following myocardial infarction. In light of this finding, we generated H19 knockout mice to further investigate the functionality of H19 and we found that cardiac fibrosis was attenuated in these mice. Altogether, these findings suggested that H19 is a fibrosis regulator during cardiac remodeling process after infarction. Due to the multiple regulatory roles of lncRNAs, we then took advantage of chromatin isolation by RNA purification (ChIRP) to identify the H19-interacting protein, YB-1. Surprisingly, mice with YB-1 knockdown displayed severe cardiac fibrosis even without injury. Furthermore, we demonstrated that YB-1 is a transcriptional suppressor of collagen 1A1. Knockout of H19 in YB-1 knockdown partially suppressed Col1a1 expression, which suggests a negative regulatory role of H19 on YB-1 towards the expression of Col1a1. Taking into account all of these findings, we concluded that H19 mediates collagen expression in fibroblasts through the inhibition of YB-1 activity during cardiac remodeling.

scholarly journals Long Noncoding RNA EZR-AS1 Regulates the Proliferation, Migration, and Apoptosis of Human Venous Endothelial Cells via SMYD3

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ganhua You ◽  
Xiangshu Long ◽  
Fang Song ◽  
Jing Huang ◽  
Maobo Tian ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Opposite Effect ◽  
Histone H3 ◽  
Noncoding Rnas

Numerous studies have shown that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of human cardiovascular diseases. However, whether lncRNA ezrin antisense RNA 1 (EZR-AS1) is associated with the progression of coronary heart disease (CHD) remains unclear. Accordingly, the aim of the present study was to evaluate the role of lncRNA EZR-AS1 in patients with CHD and in human venous endothelial cells (HUVECs). The findings revealed that lncRNA EZR-AS1 was highly expressed in the peripheral blood of patients with CHD. In vitro experiments showed that the overexpression of EZR-AS1 could enhance proliferation, migration, and apoptosis by upregulating the expression of EZR in HUVECs; downregulation of lncRNA EZR-AS1 resulted in the opposite effect. lncRNA EZR-AS1 was also found to regulate SET and MYND domain-containing protein 3 (SMYD3), a histone H3 lysine 4-specific methyltransferase, which subsequently mediated EZR transcription. Collectively, these results demonstrate that lncRNA EZR-AS1 plays an important role in HUVECs function via SMYD3 signaling.

scholarly journals The Central Roles of Noncoding RNA in Estrogen-Dependent Female Reproductive System Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jiajie Tu ◽  
Huan Yang ◽  
Lei Jiang ◽  
Yu Chen ◽  
Yu Chen ◽  
...  
Keyword(s):  
Reproductive System ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Future Research ◽  
Female Reproductive System ◽  
Research Directions ◽  
New Ideas ◽  
Future Research Directions

The pathogenesis of ovarian and endometrial cancers is closely associated with estrogen-related pathways. These estrogen-dependent tumors seriously threaten the health and quality of life in women. Noncoding RNAs (ncRNAs) are defined as RNAs that do not encode proteins, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which have been reported in estrogen-dependent female reproductive system tumors. This review systematically summarizes the role of ncRNAs in estrogen-dependent tumors and common patterns of regulatory mechanisms to explore their future research directions in tumor diagnosis, treatment, and prognosis. This may provide new ideas for the potential application of ncRNAs in estrogen-dependent female reproductive system tumors.

scholarly journals Noncoding RNAs in Cardiovascular Disease: Current Knowledge, Tools and Technologies for Investigation, and Future Directions: A Scientific Statement From the American Heart Association

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Saumya Das ◽  
Ravi Shah ◽  
Stefanie Dimmeler ◽  
Jane E. Freedman ◽  
Christopher Holley ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Noncoding Rna ◽  
Functional Role ◽  
Unmet Need ◽  
Noncoding Rnas ◽  
Rapid Expansion ◽  
Cardiovascular Development ◽  
Computational Tools ◽  
Cellular Processes

Background: The discovery that much of the non–protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion in the development of tools and technologies to investigate the role of these noncoding RNAs in cardiovascular health. Furthermore, identifying noncoding RNAs for targeted therapeutics to treat cardiovascular disease is an emerging area of research. The purpose of this statement is to review existing literature, offer guidance on tools and technologies currently available to study noncoding RNAs, and identify areas of unmet need. Methods: The writing group used systematic literature reviews (including MEDLINE, Web of Science through 2018), expert opinion/statements, analyses of databases and computational tools/algorithms, and review of current clinical trials to provide a broad consensus on the current state of the art in noncoding RNA in cardiovascular disease. Results: Significant progress has been made since the initial studies focusing on the role of miRNAs (microRNAs) in cardiovascular development and disease. Notably, recent progress on understanding the role of novel types of noncoding small RNAs such as snoRNAs (small nucleolar RNAs), tRNA (transfer RNA) fragments, and Y-RNAs in cellular processes has revealed a noncanonical function for many of these molecules. Similarly, the identification of long noncoding RNAs that appear to play an important role in cardiovascular disease processes, coupled with the development of tools to characterize their interacting partners, has led to significant mechanistic insight. Finally, recent work has characterized the unique role of extracellular RNAs in mediating intercellular communication and their potential role as biomarkers. Conclusions: The rapid expansion of tools and pipelines for isolating, measuring, and annotating these entities suggests that caution in interpreting results is warranted until these methodologies are rigorously validated. Most investigators have focused on investigating the functional role of single RNA entities, but studies suggest complex interaction between different RNA molecules. The use of network approaches and advanced computational tools to understand the interaction of different noncoding RNA species to mediate a particular phenotype may be required to fully comprehend the function of noncoding RNAs in mediating disease phenotypes.

scholarly journals Small Noncoding RNA CjNC110 Influences Motility, Autoagglutination, AI-2 Localization, Hydrogen Peroxide Sensitivity, and Chicken Colonization in Campylobacter jejuni

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Amanda J. Kreuder ◽  
Brandon Ruddell ◽  
Kathy Mou ◽  
Alan Hassall ◽  
Qijing Zhang ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Quorum Sensing ◽  
Campylobacter Jejuni ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Wild Type ◽  
Content Type ◽  
Zoonotic Pathogen ◽  
Small Noncoding Rnas

ABSTRACT Small noncoding RNAs (ncRNAs) are involved in many important physiological functions in pathogenic microorganisms. Previous studies have identified the presence of noncoding RNAs in the major zoonotic pathogen Campylobacter jejuni; however, few have been functionally characterized to date. CjNC110 is a conserved ncRNA in C. jejuni, located downstream of the luxS gene, which is responsible for the production of the quorum sensing molecule autoinducer-2 (AI-2). In this study, we utilized strand specific high-throughput RNAseq to identify potential targets or interactive partners of CjNC110 in a sheep abortion clone of C. jejuni. These data were then utilized to focus further phenotypic evaluation of the role of CjNC110 in motility, autoagglutination, quorum sensing, hydrogen peroxide sensitivity, and chicken colonization in C. jejuni. Inactivation of the CjNC110 ncRNA led to a statistically significant decrease in autoagglutination ability as well as increased motility and hydrogen peroxide sensitivity compared to the wild-type. Extracellular AI-2 detection was decreased in ΔCjNC110; however, intracellular AI-2 accumulation was significantly increased, suggesting a key role of CjNC110 in modulating the transport of AI-2. Notably, ΔCjNC110 also showed a decreased ability to colonize chickens. Complementation of CjNC110 restored all phenotypic changes back to wild-type levels. The collective results of the phenotypic and transcriptomic changes observed in our data provide valuable insights into the pathobiology of C. jejuni sheep abortion clone and strongly suggest that CjNC110 plays an important role in the regulation of energy taxis, flagellar glycosylation, cellular communication via quorum sensing, oxidative stress tolerance, and chicken colonization in this important zoonotic pathogen.

scholarly journals Could the Epigenetics of Eosinophils in Asthma and Allergy Solve Parts of the Puzzle?

2021 ◽  
Vol 22 (16) ◽  
pp. 8921
Author(s):  
Émile Bélanger ◽  
Catherine Laprise
Keyword(s):  
Dna Methylation ◽  
Social Factors ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Allergic Diseases ◽  
Epigenetic Mechanisms ◽  
Cell Type ◽  
Asthma And Allergy ◽  
Allergies And Asthma

Epigenetics is a field of study investigating changes in gene expression that do not alter the DNA sequence. These changes are often influenced by environmental or social factors and are reversible. Epigenetic mechanisms include DNA methylation, histone modification, and noncoding RNA. Understanding the role of these epigenetic mechanisms in human diseases provides useful information with regard to disease severity and development. Several studies have searched for the epigenetic mechanisms that regulate allergies and asthma; however, only few studies have used samples of eosinophil, a proinflammatory cell type known to be largely recruited during allergic or asthmatic inflammation. Such studies would enable us to better understand the factors that influence the massive recruitment of eosinophils during allergic and asthmatic symptoms. In this review, we sought to summarize different studies that aimed to discover differential patterns of histone modifications, DNA methylation, and noncoding RNAs in eosinophil samples of individuals with certain diseases, with a particular focus on those with asthma or allergic diseases.

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