scholarly journals Dynamic expression of long noncoding RNAs reveals their potential roles in spermatogenesis and fertility†

2017 ◽  
Vol 97 (2) ◽  
pp. 313-323 ◽  
Author(s):  
Lauren Wichman ◽  
Saigopal Somasundaram ◽  
Christine Breindel ◽  
Dana M. Valerio ◽  
John R. McCarrey ◽  
...  

Abstract Mammalian reproduction requires that males and females produce functional haploid germ cells through complex cellular differentiation processes known as spermatogenesis and oogenesis, respectively. While numerous studies have functionally characterized protein-coding genes and small noncoding RNAs (microRNAs and piRNAs) that are essential for gametogenesis, the roles of regulatory long noncoding RNAs (lncRNAs) are yet to be fully characterized. Previously, we and others have demonstrated that intergenic regions of the mammalian genome encode thousands of long noncoding RNAs, and many studies have now demonstrated their critical roles in key biological processes. Thus, we postulated that some lncRNAs may also impact mammalian spermatogenesis and fertility. In this study, we identified a dynamic expression pattern of lncRNAs during murine spermatogenesis. Importantly, we identified a subset of lncRNAs and very few mRNAs that appear to escape meiotic sex chromosome inactivation, an epigenetic process that leads to the silencing of the X- and Y-chromosomes at the pachytene stage of meiosis. Further, some of these lncRNAs and mRNAs show a strong testis expression pattern suggesting that they may play key roles in spermatogenesis. Lastly, we generated a mouse knockout of one X-linked lncRNA, Tslrn1 (testis-specific long noncoding RNA 1), and found that males carrying a Tslrn1 deletion displayed normal fertility but a significant reduction in spermatozoa. Our findings demonstrate that dysregulation of specific mammalian lncRNAs is a novel mechanism of low sperm count or infertility, thus potentially providing new biomarkers and therapeutic strategies.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 251.1-251
Author(s):  
J. M. Kim ◽  
H. J. Kang ◽  
S. J. Jung ◽  
B. W. Song ◽  
H. J. Jeong ◽  
...  

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Zhang ◽  
Xianwu Chen ◽  
Juntao Lin ◽  
Xiaodong Jin

AbstractBladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.


RSC Advances ◽  
2019 ◽  
Vol 9 (61) ◽  
pp. 35624-35635 ◽  
Author(s):  
Hui Zhao ◽  
Li Meng ◽  
Chengyang Xu ◽  
Bin Lin ◽  
Xiangming Zheng ◽  
...  

Long noncoding RNAs have been widely accepted to play important roles in acute myocardial infarction (AMI).


2020 ◽  
Vol 126 (9) ◽  
pp. 1127-1145 ◽  
Author(s):  
Nicolas Jaé ◽  
Stefanie Dimmeler

The advent of deep sequencing technologies led to the identification of a considerable amount of noncoding RNA transcripts, which are increasingly recognized for their functions in controlling cardiovascular diseases. MicroRNAs have already been studied for a decade, leading to the identification of several vasculoprotective and detrimental species, which might be considered for therapeutic targeting. Other noncoding RNAs such as circular RNAs, YRNAs, or long noncoding RNAs are currently gaining increasing attention, and first studies provide insights into their functions as mediators or antagonists of vascular diseases in vivo. The present review article will provide an overview of the different types of noncoding RNAs controlling the vasculature and focus on the developing field of long noncoding RNAs.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Poller ◽  
A.W Kuss ◽  
S Weiss ◽  
A Haghikia ◽  
M Gast ◽  
...  

Abstract Background Uncontrolled inflammation is a key driver of atherosclerosis, myocardial infarction (MI), and multiple other diseases. Beyond proteins and microRNAs, long noncoding RNAs (lncRNAs) are implicated in inflammation control. We previously reported suppression of lncRNA NEAT1 in circulating immune cells of post-MI patients. In mice lacking lncRNAs NEAT1 or MALAT1 we observed major immune disturbances affecting monocyte-macrophage and T cell differentiation and rendering the immune system unstable and highly vulnerable to immune stress. Here, we report functions of a novel tRNA-type transcript arising from the NEAT1-MALAT1 gene cluster, and on genetic heterogeneity of this region in the human population. Methods and results While previously investigated mice were deficient in the entire NEAT1 or MALAT1 locus, we here aimed to selectively disrupted only the novel 59-nt tRNA-like transcript “menRNA” with hitherto unknown functions. Through CRISPR/Cas9 editing we developed 4 human THP-1 monocyte-macrophage cell line clones with deletions of different extension all of which prevented, however, normal transcript folding and formation of “menRNA”. Transcriptome mapping of all clones by RNA-sequencing identified dysregulation of innate immunity-related genes (IFI16, IFITM3, IRAK3, IRF2BP2, IRF3), chemokine and interleukin receptors (CCR10, IL11RA, IL12RB2, IL23A), cell surface receptors (CD37, CD40LG, CD72, FOCAD, ITGA6, MAEA, THY1), macrophage function-associated genes (ELANE, GRN, MIF, MMP25, MST1P2, PRTN3), tRNA-processing transcripts (GARS, QRSL1P3, QTRT1P1, THG1L, VARS), and small nucleolar RNAs (SNORA26.62.64, SNORD65.112). These data and functional assays indicate functions of NEAT1-derived “menRNA” distinct from those previously described for MALAT1-derived mascRNA. As multiple data suggest inflammation control functions of the NEAT1-MALAT1 region, we investigated the extent of genetic variability of this region in humans. In cohorts from the SHIP study coordinated by the Institute for Community Medicine Greifswald, screening of this region for sequence variants and possible phenotype associations was conducted the results of which are given in Figure 1. Consistent with prior findings, a MALAT1 SNP with very low minor allele frequency (MAF=0.01) was associated (p=0.0062) with systemic low level inflammation (CRP >3.0 mg/L). Unexpected was the association (p<0.01) of eight SNPs (low MAF=0.09 for all) with BMI >35 kg/m2 and LDL >164 mg/dl. Conclusions First, selective disruption of menRNA formation in human monocyte-macrophages provides evidence that this novel type of noncoding RNA has immunoregulatory functions. Second, the phenotype associations of SNPs within the NEAT1-MALAT1 gene cluster warrant further in-depth investigation of the molecular basis of these associations, and of their allele frequencies in cardiovascular disease patient cohorts. The first three and the last authors contributed equally to this work. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): “Transcriptome analysis of circulating immune cells to improve the assessment of prognosis and the response to novel anti-inflammatory treatments after myocardial infarction”; DZHK Shared Expertise project B19-006_SE FKZ 81X2100257


2015 ◽  
Vol 9 ◽  
Author(s):  
Jesper L. V. Maag ◽  
Debabrata Panja ◽  
Ida Sporild ◽  
Sudarshan Patil ◽  
Dominik C. Kaczorowski ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  

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.


2021 ◽  
Vol 25 (04) ◽  
pp. 777-785
Author(s):  
Jingai Tan

Rice seed development involves an intricate regulatory network that directly determines seed size and weight. Long noncoding RNAs (lncRNAs) have been defined as key regulators of gene expression involved in diverse biological processes. However, the function of lncRNAs in rice seed development is still poorly understood. We performed paired-end RNA sequencing of Nipponbare rice at 5, 10 and 15 DPA (days post anthesis) in two different environments (early and middle-season rice). A total of 382 lncRNAs were detected as differentially expressed among these stages, including 344 and 307 lncRNAs in early and middle-season rice, respectively, and 70.42% (269 of 382) of the lncRNAs were found in both environments. The results showed that environment had little effect on the expression of lncRNAs. Furthermore, there were 127, 172, and 31 DElncs (differentially expressed lncRNAs) and 154, 140, and 59 DElncs in early and middle-season rice, respectively, in comparisons of 10_DPA vs 5_DPA, 15_DPA vs 5_DPA and 15_DPA vs 10_DPA. This result indicated that the number and expression level of lncRNAs at 5 DAP were significantly different from those at 10 DAP and 15 DAP. Furthermore, GO pathway analysis of cis target genes of DElncs in 10_DPA vs 5_DPA and 15_DPA vs 5_DPA revealed that the significant GO pathways were extracellular region, nutrient reservoir activity and cell wall macromolecule catabolic process. Our study revealed dynamic expression of lncRNAs in three stages and systematically explored the differences in lncRNAs between early and middle-season rice, which could provide a valuable resource for future high-yield breeding. © 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers © 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers© 2021 Friends Science Publishers©


2017 ◽  
Vol 45 (5) ◽  
pp. 1117-1124 ◽  
Author(s):  
Petr Svoboda

Oocyte-to-embryo transition is a process during which an oocyte ovulates, is fertilized, and becomes a developing embryo. It involves the first major genome reprogramming event in life of an organism where gene expression, which gave rise to a differentiated oocyte, is remodeled in order to establish totipotency in blastomeres of an early embryo. This remodeling involves replacement of maternal RNAs with zygotic RNAs through maternal RNA degradation and zygotic genome activation. This review is focused on expression and function of long noncoding RNAs (lncRNAs) and small RNAs during oocyte-to-embryo transition in mammals. LncRNAs are an assorted rapidly evolving collection of RNAs, which have no apparent protein-coding capacity. Their biogenesis is similar to mRNAs including transcriptional control and post-transcriptional processing. Diverse molecular and biological roles were assigned to lncRNAs although most of them probably did not acquire a detectable biological role. Since some lncRNAs serve as precursors for small noncoding regulatory RNAs in RNA silencing pathways, both types of noncoding RNA are reviewed together.


2016 ◽  
Vol 29 (3) ◽  
pp. 155-155
Author(s):  
John P. Carr ◽  
Steven A. Whitham

Investigations in recent years have uncovered important roles for RNA molecules that do not encode proteins (‘noncoding RNAs’) but which, nevertheless, exert powerful effects on gene expression at both transcriptional and posttranscriptional levels. Our late colleague Biao Ding, who died unexpectedly on June 25, 2015, proposed a Focus Issue on the roles in plant-microbe interactions of noncoding RNAs, whether of plant or microbial origin and including small interfering (si)RNAs, microRNAs, phased siRNAs, and long noncoding RNAs, as well as viroids and satellite RNAs. The Editorial Board of MPMI has decided to dedicate this Focus Issue to the memory of Professor Biao Ding, a valued and deeply missed colleague and friend.


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