RNA & disease (Houston, Tex.)最新文献

Analysis of RNA Exosome Subunit Transcript Abundance Across Tissues: Implications for Neurological Disease Pathogenesis RNA外泌体亚基转录物在组织中的丰度分析:对神经系统疾病发病机制的影响

RNA & disease (Houston, Tex.) Pub Date : 2023-01-01 DOI: 10.14800/rd.1247

{"title":"Analysis of RNA Exosome Subunit Transcript Abundance Across Tissues: Implications for Neurological Disease Pathogenesis","authors":"","doi":"10.14800/rd.1247","DOIUrl":"https://doi.org/10.14800/rd.1247","url":null,"abstract":"Exosomopathies are a collection of rare diseases caused by mutations in genes that encode structural subunits of a ribonuclease complex termed the RNA exosome. The RNA exosome mediates both RNA processing and degradation of multiple classes of RNA. This complex is evolutionarily conserved and required for fundamental cellular functions, including rRNA processing. Recently, missense mutations in genes encoding structural subunits of the RNA exosome complex have been linked to a variety of distinct neurological diseases, many of them childhood neuronopathies with at least some cerebellar atrophy. Understanding how these missense mutations lead to the disparate clinical presentations that have been reported for this class of diseases necessitates investigation of how these specific changes alter cell-specific RNA exosome function. Although the RNA exosome complex is routinely referred to as ubiquitously expressed, little is known about the tissue- or cell-specific expression of the RNA exosome complex or any individual subunit. Here, we leverage publicly available RNA-sequencing data to analyze RNA exosome subunit transcript levels in healthy human tissues, focusing on those tissues that are impacted in exosomopathy patients described in clinical reports. This analysis provides evidence to support the characterization of the RNA exosome as ubiquitously expressed with transcript levels for the individual subunits that vary in different tissues. However, the cerebellar hemisphere and cerebellum have high levels of nearly all RNA exosome subunit transcripts. These findings could suggest that the cerebellum has a high requirement for RNA exosome function and potentially explain why cerebellar pathology is common in RNA exosomopathies.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136002669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling Pathogenic Variants in the RNA Exosome. 在RNA外泌体中建模致病变异。

RNA & disease (Houston, Tex.) Pub Date : 2020-01-01

Julia de Amorim, Anne Slavotinek, Milo B Fasken, Anita H Corbett, Derrick J Morton

{"title":"Modeling Pathogenic Variants in the RNA Exosome.","authors":"Julia de Amorim, Anne Slavotinek, Milo B Fasken, Anita H Corbett, Derrick J Morton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Exosomopathies are a collection of rare diseases caused by mutations in genes that encode structural subunits of the RNA exosome complex (EXOSC). The RNA exosome is critical for both processing and degrading many RNA targets. Mutations in individual RNA exosome subunit genes (termed EXOSC genes) are linked to a variety of distinct diseases. These exosomopathies do not arise from homozygous loss-of-function or large deletions in the EXOSC genes likely because some level of RNA exosome activity is essential for viability. Thus, all patients described so far have at least one allele with a missense mutation encoding an RNA exosome subunit with a single pathogenic amino acid change linked to disease. Understanding how these changes lead to the disparate clinical presentations that have been reported for this class of diseases necessitates investigation of how individual pathogenic missense variants alter RNA exosome function. Such studies will require access to patient samples, a challenge for these very rare diseases, coupled with modeling the patient variants. Here, we highlight five recent studies that model pathogenic variants in EXOSC3, EXOSC2, and EXOSC5.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"7 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528344/pdf/nihms-1703784.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39541819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long Non-coding RNA Landscape in Colorectal Cancer 结直肠癌中的长链非编码RNA景观

RNA & disease (Houston, Tex.) Pub Date : 2018-03-09 DOI: 10.14800/RD.3

M. S. Ong, Wanpei Cai, T. Tan, R. Huang, S. Hooi, C. Yap, A. Kumar

引用次数: 6

MicroRNA-7: A critical sensitizer for TRAIL sensitivity in glioblastoma cells MicroRNA-7：胶质母细胞瘤细胞TRAIL敏感性的关键增敏剂

RNA & disease (Houston, Tex.) Pub Date : 2018-01-15 DOI: 10.14800/RD.1620

Xiao Zhang, A. Yang, Rui Zhang

引用次数: 1

Implication of obesity-induced miR-96 in hepatic insulin resistance 肥胖诱导的miR-96在肝脏胰岛素抵抗中的意义

RNA & disease (Houston, Tex.) Pub Date : 2017-12-04 DOI: 10.14800/RD.1615

K. Min, Yi-Seul Son, Won-Mo Yang, Wan Lee

{"title":"Implication of obesity-induced miR-96 in hepatic insulin resistance","authors":"K. Min, Yi-Seul Son, Won-Mo Yang, Wan Lee","doi":"10.14800/RD.1615","DOIUrl":"https://doi.org/10.14800/RD.1615","url":null,"abstract":"Obesity is a serious health problem that is caused by an equilibrium shift towards elevated energy intake over expenditure, and is often involved in a range of metabolic diseases. A diet rich in saturated fatty acids (SFA), which is one of the leading causes of obesity and ectopic lipid accumulation in the key organs for metabolic regulation, results in an imbalance of the cellular metabolism and an inadequate response of hepatocytes to insulin, which is known as hepatic insulin resistance. Although endogenous non-coding small microRNAs (miRNAs) play important roles in the post-transcriptional repression of the target genes, the implications of obesity-induced miRNAs in metabolic diseases, particularly in the development of hepatic insulin resistance, are largely unknown. In recent studies, SFA and a high fat diet were found to increase the expression of certain miRNAs significantly in the liver and skeletal muscle. These obesity-induced miRNAs were also up-regulated in human subjects with metabolic diseases. Our recent study highlights a novel mechanism whereby miR-96, which is one of the obesity-induced miRNA, participates actively in the development of hepatic insulin resistance in obesity. Studies focusing on obesity-induced miR-96 have indicated the strong diagnostic and therapeutic importance of miRNAs in insulin resistance and metabolic diseases. This will also help better understand the pathogenesis of insulin resistance and T2DM in obesity, and enable the development of inhibitors against obesity-induced miRNAs as a novel diagnostic and therapeutic strategy for metabolic diseases.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48421661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reciprocal Regulation among miR-181d/CRY2/FBXL3/c-myc Signaling Axis Modulates Metabolism in Colorectal Cancer miR-181d／CRY2／FBXL3／c-myc信号轴对癌症大肠癌代谢的相互调节

RNA & disease (Houston, Tex.) Pub Date : 2017-11-20 DOI: 10.14800/RD.1613

Xiao-Zhong Guo, Xuehui Hong

{"title":"Reciprocal Regulation among miR-181d/CRY2/FBXL3/c-myc Signaling Axis Modulates Metabolism in Colorectal Cancer","authors":"Xiao-Zhong Guo, Xuehui Hong","doi":"10.14800/RD.1613","DOIUrl":"https://doi.org/10.14800/RD.1613","url":null,"abstract":"Patients with CRC (colorectal cancer) usually have a poor prognosis and the cure rate of CRC remained unsatisfied due to unfavorable curative effect. It is well known that microRNAs (miRNAs) and energy metabolism have pivotal roles in CRC progression. In a recent article in Cell Death & Disease by Xiaofeng Guo. et al. 2017, we have reported an oncogenic role of miR-181d in CRC by promoting glycolysis, and its underlying molecular mechanism about a new feedback loop among miR-181d/CRY2/FBXL3/c-myc signaling axis. Among these, we have identified the level of miR-181d was upregulated in CRC and the inhibition of miR-181d decreased glycolysis in CRC cells. We also found that c-myc played a central role in regulating cell glycolysis, which is required for the metabolic shift induced by miR-181d. Besides, we have demonstrated FBXL3 and CRY2 were direct targets of miR-181d and c-myc promoted miR-181d upregulation while inhibiting the expression of CRY2 and FBXL3 in CRC cells. The data from our recent article strongly suggest a new light onto the oncogenic function of the miR-181d in CRC. Furthermore, these findings represent a novel potential approach for silencing miR-181d/c-myc signaling pathway in CRC treatment.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42390440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA analysis of colorectal cancer using fecal and tissue samples 使用粪便和组织样本对癌症大肠癌的微小RNA分析

RNA & disease (Houston, Tex.) Pub Date : 2017-09-11 DOI: 10.14800/rd.1592

N. Yamazaki, Y. Koga, Y. Matsumura

{"title":"MicroRNA analysis of colorectal cancer using fecal and tissue samples","authors":"N. Yamazaki, Y. Koga, Y. Matsumura","doi":"10.14800/rd.1592","DOIUrl":"https://doi.org/10.14800/rd.1592","url":null,"abstract":"Recently, several microRNAs (miRNAs) have been reported as promising biomarkers for cancer detection and tumor recurrence risk. Due to its stability, miRNA can be accessed from samples stored in severe conditions, such as feces or formalin-fixed paraffin-embedded (FFPE) tissue. Fecal miRNA extracted from the residuum of fecal occult blood tests (FOBTs) was assessed to determine whether a combination of this fecal miRNA test (FmiRT) with FOBT could improve the false-negative rate of colorectal cancer (CRC) screening compared with FOBT alone. Expression of miR-106a in patients with both positive and negative FOBTs was significantly higher than in healthy volunteers. To identify a high-risk group for recurrence, miRNAs were extracted from FFPE samples of patients with stage II CRC. Tumor recurrence occurred at a significantly higher rate in patients with increased miR-181c expression than in those with lower expression. The recurrence rate in patients with stage II CRC with higher expression of miR-181c was similar to that of patients with stage III CRC who had been treated by surgical resection alone. As miRNAs are stable in several severe storage conditions, such as in fecal and FFPE samples, they could be valuable, accessible biomarkers for CRC, for use both in cancer screening and as predictors of recurrence.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44011106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KSHV Episomes: Rugged Individualists on the Factory Floor KSHV书信集：工厂里坚韧不拔的个人主义者

RNA & disease (Houston, Tex.) Pub Date : 2017-06-26 DOI: 10.14800/RD.1565

M. Campbell, C. Chen, Y. Izumiya

{"title":"KSHV Episomes: Rugged Individualists on the Factory Floor","authors":"M. Campbell, C. Chen, Y. Izumiya","doi":"10.14800/RD.1565","DOIUrl":"https://doi.org/10.14800/RD.1565","url":null,"abstract":"We have recently developed tools to study Kaposi’s sarcoma-associated virus (KSHV) reactivation at the single-episome level. Using immunofluorescent labeling of latent nuclear antigen (LANA) protein to localize viral episomes, combined with fluorescence in situ RNA hybridization (RNA-FISH) of an intron region of immediate early transcripts, we have visualized active transcription of viral genomes in infected cells. At this level, we observed that not all episomes within a single cell were uniformly transcribed following reactivation stimuli. However, those episomes that were transcribed, formed large aggregates containing a significant fraction of cellular RNA polymerase II (RNAPII), foci consistent with previously described viral transcriptional factories. This focal assembly of RNAPII on viral episomes was accompanied by an overall decrease in the pool of cellular RNAPII. Additionally, the viral transcriptional factories localized with replicating viral genomic DNAs. This co-localization suggests that KSHV may assemble an “all-in-one” workroom for both gene transcription and DNA replication. While previous studies have reported on the variable response of individual KSHV infected cells or episomes derived from a population during reactivation, our results expose this variation further by demonstrating heterogeneity in the response of individual KSHV episomes within a single reactivating cell.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46870029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA methylation in lymphoid malignancies 淋巴细胞恶性肿瘤中的RNA甲基化

RNA & disease (Houston, Tex.) Pub Date : 2017-06-19 DOI: 10.14800/RD.1563

Senthil R Kumar, K. Taylor, J. Bryan, A. M. Eaton

{"title":"RNA methylation in lymphoid malignancies","authors":"Senthil R Kumar, K. Taylor, J. Bryan, A. M. Eaton","doi":"10.14800/RD.1563","DOIUrl":"https://doi.org/10.14800/RD.1563","url":null,"abstract":"N 6 -methyl-adenosine (m 6 A) modification is the most abundant internal modification in mammalian RNA and plays an important role in gene expression mechanisms such as mRNA splicing, nuclear export, transcript stability and translational efficiency. The extent and the significance of m 6 A modifications in pathological conditions, especially hematological malignancies such as lymphomas are not known. In this study, the global m 6 A methylation by an immunocapture method in normal B cells (GMO 6990), and in the B cell neoplastic cells such as diffuse large B cell lymphoma (DB), Burkitt’s lymphoma (Raji) and a relapsed pre-B cell acute lymphoblastic leukemia (ALL) (NALM6) cells are discussed. Variable mRNA expression of RNA methylases such as methyltransferase like 3 (METTL3) and Wilms tumor 1 associated protein (WTAP) that methylates internal adenosine residues in mRNA was observed in normal and lymphoma cells as quantified by qRT-PCR. Further, an mRNA demethylase, Fat mass and obesity associated enzyme (FTO) mRNA expression was found to be high in lymphoma cells compared to normal B cells. A similar trend was also observed between normal and ALL patients at diagnosis. Overall, our studies suggest that altered RNA methylation and enzymes controlling this process may be of significance in the pathology of lymphoid malignancies.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48150396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors 一个适体，两种功能:全长适体抑制AMPA受体，而短的适体同时抑制AMPA和盐酸盐受体

RNA & disease (Houston, Tex.) Pub Date : 2017-06-12 DOI: 10.14800/RD.1560

William J. Jaremko, Zhen-Hua Huang, Wei Wen, Andrew Wu, Nicholas Karl, L. Niu

{"title":"One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors","authors":"William J. Jaremko, Zhen-Hua Huang, Wei Wen, Andrew Wu, Nicholas Karl, L. Niu","doi":"10.14800/RD.1560","DOIUrl":"https://doi.org/10.14800/RD.1560","url":null,"abstract":"AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74875115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7