scholarly journals Dystrophin in the Neonatal and Adult Rat Intestine

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1155
Author(s):  
Judith M. Lionarons ◽  
Govert Hoogland ◽  
Rutger J. Slegers ◽  
Hellen Steinbusch ◽  
Sandra M. H. Claessen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Smooth Muscle Actin ◽  
Muscularis Propria ◽  
Rat Intestine ◽  
Adult Rats ◽  
Distal Intestine ◽  
Adult Rat

Background: Gastrointestinal (GI) complaints are frequently noted in aging dystrophinopathy patients, yet their underlying molecular mechanisms are largely unknown. As dystrophin protein isoform 71 (Dp71) is particularly implicated in the development of smooth muscle cells, we evaluated its distribution in the neonatal and adult rat intestine in this study. Methods: Dp71 expression levels were assessed in the proximal (duodenum, jejunum and ileum) and distal (caecum, colon and rectum) intestine by Western blotting and qPCR. In addition, the cellular distribution of total Dp was evaluated in the duodenum and colon by immunohistochemical colocalization studies with alpha-smooth muscle actin (aSMA), Hu RNA binding proteins C and D (HuC/HuD) for neurons and vimentin (VIM) for interstitial cells. Results: In neonatal and adult rats, the distal intestine expressed 2.5 times more Dp71 protein than the proximal part (p < 0.01). This regional difference was not observed in Dp71 mRNA. During both stages, Dp-immunoreactivity was predominant in the muscularis propria, where it co-localized with aSMA and HuC/HuD. Conclusions: In neonatal and adult rats, Dp71 was expressed highest in the distal intestine. Together with the observation that Dp may be expressed by myenteric neurons, this warrants a paradigm shift in the treatment of GI comorbidities.

scholarly journals Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Long ◽  
Zhi Lin ◽  
Liang Li ◽  
Min Ma ◽  
Zhixing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Future Perspectives ◽  
Cis Acting ◽  
New Class ◽  
Functional Peptides ◽  
Mirna Sponges

AbstractColorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

scholarly journals The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

2011 ◽  
Vol 22 (16) ◽  
pp. 2875-2885 ◽  
Author(s):  
Mai Nguyen Chi ◽  
Jacques Auriol ◽  
Bernard Jégou ◽  
Dimitris L. Kontoyiannis ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Germ Cells ◽  
Posttranscriptional Regulation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Female Sterility ◽  
Targeted Deletion

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

scholarly journals High-resolution mapping of cis-regulatory variation in budding yeast

2017 ◽  
Vol 114 (50) ◽  
pp. E10736-E10744 ◽  
Author(s):  
Ryosuke Kita ◽  
Sandeep Venkataram ◽  
Yiqi Zhou ◽  
Hunter B. Fraser
Keyword(s):  
High Resolution ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Sign Test ◽  
Eqtl Mapping ◽  
Regulatory Variation ◽  
Conserved Genes ◽  
Causal Variants ◽  
Resolution Mapping

Genetic variants affecting gene-expression levels are a major source of phenotypic variation. The approximate locations of these variants can be mapped as expression quantitative trait loci (eQTLs); however, a major limitation of eQTLs is their low resolution, which precludes investigation of the causal variants and their molecular mechanisms. Here we report RNA-seq and full genome sequences for 85 diverse isolates of the yeast Saccharomyces cerevisiae—including wild, domesticated, and human clinical strains—which allowed us to perform eQTL mapping with 50-fold higher resolution than previously possible. In addition to variants in promoters, we uncovered an important role for variants in 3′UTRs, especially those affecting binding of the PUF family of RNA-binding proteins. The eQTLs are predominantly under negative selection, particularly those affecting essential genes and conserved genes. However, applying the sign test for lineage-specific selection revealed the polygenic up-regulation of dozens of biofilm suppressor genes in strains isolated from human patients, consistent with the key role of biofilms in fungal pathogenicity. In addition, a single variant in the promoter of a biofilm suppressor, NIT3, showed the strongest genome-wide association with clinical origin. Altogether, our results demonstrate the power of high-resolution eQTL mapping in understanding the molecular mechanisms of regulatory variation, as well as the natural selection acting on this variation that drives adaptation to environments, ranging from laboratories to vineyards to the human body.

scholarly journals Expression of α-smooth muscle actin in the periodontal ligament during post-emergent tooth eruption

2018 ◽  
Vol 46 (6) ◽  
pp. 2423-2435
Author(s):  
Domna Dorotheou ◽  
Marie-Luce Bochaton-Piallat ◽  
Catherine Giannopoulou ◽  
Stavros Kiliaridis
Keyword(s):  
Smooth Muscle ◽  
Periodontal Ligament ◽  
Smooth Muscle Actin ◽  
Root Apex ◽  
Tooth Eruption ◽  
Muscle Actin ◽  
Adult Rats ◽  
Time Points ◽  
Male Wistar Rats ◽  
The Right

Objective This study was performed to explore the expression of α-smooth muscle actin (α-SMA) in the periodontal ligament (PDL) of young and adult rats during post-emergent tooth eruption in opposed and unopposed teeth at two time points: 3 and 15 days after antagonist loss. Methods Four-week-old (n = 20) and 22-week-old (n = 20) male Wistar rats were used. The right maxillary molar crowns were cut down. PDL samples were isolated from the first mandibular molars at two time points: 3 and 15 days after cut-down of the right maxillary molars. Quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining were performed to detect differences in α-SMA expression in the PDL tissues of unopposed versus opposed molars. Results α-SMA was upregulated in the PDL of the unopposed molars in the 3-day group of young rats. The region around the root apex of the unopposed molars in this group exhibited strong immunostaining for α-SMA. The expression level and immunoreactivity of α-SMA did not differ in both time points in young controls and among all the adult groups. Conclusion α-SMA-positive myofibroblasts are implicated in post-emergent tooth eruption of unopposed molars of young animals.

The development expression of the rat alpha-vascular and gamma-enteric smooth muscle isoactins: isolation and characterization of a rat gamma-enteric actin cDNA

1988 ◽  
Vol 8 (12) ◽  
pp. 5224-5231
Author(s):  
K M McHugh ◽  
J L Lessard
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
The Other ◽  
Single Amino Acid ◽  
Cdna Clones ◽  
Muscle Actin ◽  
Adult Rats ◽  
Sequence Comparisons ◽  
Isolation And Characterization ◽  
Sequence Similarities

We have isolated and characterized two cDNA clones from whole rat stomach, pRV alpha A-19 and pRE gamma A-11, which are specific for the alpha-vascular and gamma-enteric smooth muscle isoactins, respectively. The rat gamma-enteric smooth muscle actin contains a single amino acid substitution of a proline for a glutamine at position 359 of the mature peptide when compared with the chicken gizzard gamma-actin sequence (J. Vandekerckhove and K. Weber, FEBS Lett. 102:219, 1979). Sequence comparisons of the 5' and 3' untranslated (UT) regions of the two smooth muscle actin cDNAs demonstrate that these regions contain no apparent sequence similarities. Additional comparisons of the 5' UT regions of the two smooth muscle actin cDNAs to all other known actin sequences reveal no apparent sequence similarities for the rat gamma-enteric isoactin within the 15 base pairs of sequence currently available, while the rat alpha-vascular isoactin contains two separate sequences which are similar to sequences within the 5' UT regions of the human and chicken alpha-vascular actin genes. A similar comparison of the 3' UT regions of the two smooth muscle actins demonstrates that the alpha-vascular isoactins do not contain the high degree of cross-species sequence conservation observed for the other isoactins and that the gamma-enteric isoactin contains an inverted sequence of 52 nucleotides which is similar to a sequence found within the 3' UT regions of the human, chicken, and rat beta-cytoplasmic isoactins. These observations complicate the apparent cross-species conservation of isotype specificity of these domains previously observed for the other actin isoforms. Northern blot analysis of day 15 rat embryos and newborn, day 19 postbirth, and adult rats demonstrates that the day 15 rat embryo displays low to undetectable levels of smooth muscle isoactin mRNA expression. By birth, the stomach and small intestine show dramatic increases in alpha-vascular and gamma-enteric actin expression. These initially high levels of expression decrease through day 19 to adulthood. In the adult rat, the uterus and aorta differ in their content of smooth muscle isoactin mRNA. These results demonstrate that the gamma-enteric and alpha-vascular isoactin mRNAs are coexpressed to various degrees in tissues which contain smooth muscle.

The expanding world of metabolic enzymes moonlighting as RNA binding proteins

2021 ◽  
Author(s):  
Nicole J. Curtis ◽  
Constance J. Jeffery
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Molecular Structures ◽  
Intermediary Metabolism ◽  
The Many ◽  
And Function

RNA binding proteins play key roles in many aspects of RNA metabolism and function, including splicing, transport, translation, localization, stability and degradation. Within the past few years, proteomics studies have identified dozens of enzymes in intermediary metabolism that bind to RNA. The wide occurrence and conservation of RNA binding ability across distant branches of the evolutionary tree suggest that these moonlighting enzymes are involved in connections between intermediary metabolism and gene expression that comprise far more extensive regulatory networks than previously thought. There are many outstanding questions about the molecular structures and mechanisms involved, the effects of these interactions on enzyme and RNA functions, and the factors that regulate the interactions. The effects on RNA function are likely to be wider than regulation of translation, and some enzyme–RNA interactions have been found to regulate the enzyme's catalytic activity. Several enzyme–RNA interactions have been shown to be affected by cellular factors that change under different intracellular and environmental conditions, including concentrations of substrates and cofactors. Understanding the molecular mechanisms involved in the interactions between the enzymes and RNA, the factors involved in regulation, and the effects of the enzyme–RNA interactions on both the enzyme and RNA functions will lead to a better understanding of the role of the many newly identified enzyme–RNA interactions in connecting intermediary metabolism and gene expression.

scholarly journals Neurogenesis: Regulation by Alternative Splicing and Related Posttranscriptional Processes

2016 ◽  
Vol 23 (5) ◽  
pp. 466-477 ◽  
Author(s):  
Enrique Lara-Pezzi ◽  
Manuel Desco ◽  
Alberto Gatto ◽  
María Victoria Gómez-Gaviro
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Protein Isoforms ◽  
Mammalian Brain ◽  
Nonsense Mediated Decay

The complexity of the mammalian brain requires highly specialized protein function and diversity. As neurons differentiate and the neuronal circuitry is established, several mRNAs undergo alternative splicing and other posttranscriptional changes that expand the variety of protein isoforms produced. Recent advances are beginning to shed light on the molecular mechanisms that regulate isoform switching during neurogenesis and the role played by specific RNA binding proteins in this process. Neurogenesis and neuronal wiring were recently shown to also be regulated by RNA degradation through nonsense-mediated decay. An additional layer of regulatory complexity in these biological processes is the interplay between alternative splicing and long noncoding RNAs. Dysregulation of posttranscriptional regulation results in defective neuronal differentiation and/or synaptic connections that lead to neurodevelopmental and psychiatric disorders.

scholarly journals TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

2015 ◽  
Vol 35 (6) ◽  
pp. 2233-2243 ◽  
Author(s):  
Yinglong Sa ◽  
Chao Li ◽  
Hongbin Li ◽  
Hailin Guo
Keyword(s):  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Human Fibroblasts ◽  
Mapk Signaling ◽  
Scar Formation ◽  
Dependent Manner ◽  
Muscle Actin ◽  
Mesenchymal Transition

Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT)-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1), Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.

P5398CircRNAs deregulation in heart failure patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Greco ◽  
A Made' ◽  
M Longo ◽  
R Tikhomirov ◽  
S Castelvecchio ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Characterization ◽  
Enrichment Analysis ◽  
Host Gene ◽  
Circular Rnas ◽  
Amplification Efficiency ◽  
Rna Seq ◽  
Bioinformatics Pipeline

Abstract Background Circular RNAs (circRNAs) are an emerging class of noncoding RNAs stemming from the splicing and circularization of pre-mRNAs exons. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. Recently, they have been found deregulated in dilated cardiomyopathies (DCM), one of the cardiovascular diseases with the worst rate of morbidity and mortality, and whose molecular mechanisms are only partially known. Purpose Therein, we will evaluate in ischemic DCM patients the modulation of 17 circRNAs, 14 out of them obtained from literature data on DCM ischemic or not, while the other 3 were circRNAs not characterized in the heart previously. The study aims to identify circRNAs candidates for further functional characterization in DCM. In addition, as differential expression (DE) analysis is not easily performed for circRNAs in RNA-seq datasets, the validated circRNAs will be used to set up the most specific and sensitive bioinformatics pipeline for circRNA-DE analysis. Methods We designed divergent and convergent specific primers for 17 circRNAs and their host gene, respectively, and their amplification efficiency was measured by RT-qPCR. Transcripts expression was measured in left ventricle biopsies of 12 patients affected by non end-stage ischemic HF and of 12 matched controls. Results We identified cPVT1, cANKRD17, cBPTF as DE, and validated the modulation of 5 out of the 14 DCM-related circRNAs (cHIPK3, cALPK2, cPCMTD1, cNEBL, cSLC8A1), while cPDRM5, cTTN1 showed opposite modulation, which may be due to the specific disease condition. All of them were modulated differently from the respective host gene. CircRNA/miRNA interactions were predicted using Starbase 3.0. Next, mRNAs-targets of the identified miRNAs were predicted by mirDIP 4.1 and intersected with gene expression datasets of the same patients, previously obtained by microarray analysis. We found that cBPTF and cANKRD17 might sponge 12 and 2 miRNAs, respectively. Enrichment analysis of the relevant targets identified several important pathways implicated in DCM, such as MAPK, FoxO, EGFR, VEGF and Insulin/IGF pathways. In addition, deep RNA-Seq analysis that is currently ongoing and the validated circRNAs will be used to optimize the bioinformatics pipeline for circRNA DE analysis. Conclusions We identified a subset of circRNAs deregulated in ischemic HF potentially implicated in HF pathogenesis.

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