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Altered localization of staufen1 in amyotrophic lateral sclerosis 肌萎缩性侧索硬化症中施陶芬1的定位改变
RNA & disease (Houston, Tex.) Pub Date : 2016-03-14 DOI: 10.14800/RD.1210
E. Perlson
{"title":"Altered localization of staufen1 in amyotrophic lateral sclerosis","authors":"E. Perlson","doi":"10.14800/RD.1210","DOIUrl":"https://doi.org/10.14800/RD.1210","url":null,"abstract":"Localized protein expression is crucial for the health and survival of axons and dendrites in a rapidly changing environment. This process, however, cannot take place without the precise spatiotemporal localization of the cellular translational machinery and of mRNA. mRNA transport and localization requires a variety of RNA-binding proteins. Here, we highlight a recent publication which presents evidence for the altered localization of the dsRNA-binding protein Staufen1 as a result of Amyotrophic Lateral Sclerosis (ALS) linked mutations, supporting the perception of ALS as a RNA spatiotemporal mislocalization disease.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657019","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
Functional interplay between PPM1G and the transcription elongation machinery PPM1G与转录延伸机制之间的功能相互作用
RNA & disease (Houston, Tex.) Pub Date : 2016-03-14 DOI: 10.14800/RD.1215
Swapna Gudipaty, Iván D’Orso
{"title":"Functional interplay between PPM1G and the transcription elongation machinery","authors":"Swapna Gudipaty, Iván D’Orso","doi":"10.14800/RD.1215","DOIUrl":"https://doi.org/10.14800/RD.1215","url":null,"abstract":"Transcription elongation is a critical regulatory step in the gene expression cycle. One key regulator of the switch between transcription initiation and elongation is the P-TEFb kinase, which phosphorylates RNA polymerase II (Pol II) and several negative elongation factors to relieve the elongation block at paused promoters to facilitate productive elongation. Here, we highlight recent findings signifying the role of the PPM1G/PP2Cγ phosphatase in activating and maintaining the active transcription elongation state by regulating the availability of P-TEFb and blocking its assembly into the catalytic inactive 7SK small nuclear ribonucleoprotein (snRNP) complex.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"164 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73478236","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: 8
Microfluidic chip with molecular beacons detects miRNAs in Human CSF to reliably characterize CNS-specific disorders 带有分子信标的微流控芯片检测人脑脊液中的mirna，以可靠地表征中枢神经系统特异性疾病
RNA & disease (Houston, Tex.) Pub Date : 2016-02-17 DOI: 10.14800/RD.1183
Sohila Zadran, F. Remacle, R. Levine
{"title":"Microfluidic chip with molecular beacons detects miRNAs in Human CSF to reliably characterize CNS-specific disorders","authors":"Sohila Zadran, F. Remacle, R. Levine","doi":"10.14800/RD.1183","DOIUrl":"https://doi.org/10.14800/RD.1183","url":null,"abstract":"RNA profiling in biofluids holds promise as both diagnostic and prognostic markers. High expression levels of distinctive cell free circulating miRNAs in serum, plasma and cerebral spinal fluid (CSF), have been utilized as classifiers to detect and characterize disorders of the central nervous system (CNS).   We formulated the quantitative theory showing how the results of surprisal analysis enable a reliable inference if tumor cells are present in the sample from a single measurement.  Subsequently, we develop a molecular beacon-based microfluidic chip that enables for fluorescence detection of miRNAs without amplification in low volumes of human CSF.  Using surprisal analysis, we identified a miRNA classifier that enables high fidelity detection and characterization of human brain tumors. We anticipate that this micro-fluidic platform will provide a critical translational tool with point of care potential for CNS disorders.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656996","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: 1
Development of a novel RNA-programmable artificial transactivator able to upregulate endogenous genes ad libitum 一种新型rna可编程人工反激活子的开发，能够随意上调内源性基因
RNA & disease (Houston, Tex.) Pub Date : 2016-01-25 DOI: 10.14800/RD.1142
Cristina Fimiani, Elisa Goina, A. Mallamaci
{"title":"Development of a novel RNA-programmable artificial transactivator able to upregulate endogenous genes ad libitum","authors":"Cristina Fimiani, Elisa Goina, A. Mallamaci","doi":"10.14800/RD.1142","DOIUrl":"https://doi.org/10.14800/RD.1142","url":null,"abstract":"Here we provide a concise overview of a new platform we recently developed for transactivating endogenous genes ad libitum. It relies on a binary design, including an RNA cofactor in charge of recognizing the target gene, and a polypeptidic apofactor stimulating transcription. Compared to similar CRISPR-based devices, our artificial transactivators are seven-folds smaller and elicit a lower, however robust and biologically effective, expression gain. Remarkably, they only work in cells which already transcribe the gene of interest. These properties make our novel platform an appealing potential tool for restoring normal expression levels of haploinsufficient genes upon generalized delivery.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656937","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
Fast-forward generation of effective artificial small RNAs for enhanced antiviral defense in plants. 快速生成有效的人工小rna以增强植物的抗病毒防御。
RNA & disease (Houston, Tex.) Pub Date : 2016-01-12 DOI: 10.14800/RD.1130
A. Carbonell, J. C. Carrington, J. Daròs
{"title":"Fast-forward generation of effective artificial small RNAs for enhanced antiviral defense in plants.","authors":"A. Carbonell, J. C. Carrington, J. Daròs","doi":"10.14800/RD.1130","DOIUrl":"https://doi.org/10.14800/RD.1130","url":null,"abstract":"Artificial small RNAs (sRNAs) are short ≈21-nt non-coding RNAs engineered to inactivate sequence complementary RNAs. In plants, they have been extensively used to silence cellular transcripts in gene function analyses and to target invading RNA viruses to induce resistance. Current artificial sRNA-based antiviral resistance in plants is mainly limited to a single virus, and is jeopardized by the emergence of mutations in the artificial sRNA target site or by the presence of co-infecting viruses. Hence, there is a need to further develop the artificial sRNA approach to generate more broad and durable antiviral resistance in plants. A recently developed toolbox allows for the time and cost-effective large-scale production of artificial sRNA constructs in plants. The toolbox includes the P-SAMS web tool for the automated design of artificial sRNAs, and a new generation of artificial microRNA and synthetic trans-acting small interfering RNA (syn-tasiRNA) vectors for direct cloning and high expression of artificial sRNAs. Here we describe how the simplicity and high-throughput capability of these new technologies should accelerate the study of artificial sRNA-based antiviral resistance in plants. In particular, we discuss the potential of the syn-tasiRNA approach as a promising strategy for developing more effective, durable and broad antiviral resistance in plants.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656927","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: 18
The levels of the RNA binding protein Hu antigen R determine the druggability of the neddylation pathway in liver cancer RNA结合蛋白Hu抗原R的水平决定了肝癌中类化修饰通路的可药性
RNA & disease (Houston, Tex.) Pub Date : 2016-01-11 DOI: 10.14800/rd.1123
M. Martínez‐Chantar, Lucía Barbier Torres, D. Ramos
{"title":"The levels of the RNA binding protein Hu antigen R determine the druggability of the neddylation pathway in liver cancer","authors":"M. Martínez‐Chantar, Lucía Barbier Torres, D. Ramos","doi":"10.14800/rd.1123","DOIUrl":"https://doi.org/10.14800/rd.1123","url":null,"abstract":"Hepatocellular carcinoma (HCC), the most common liver cancer, is an important leading cause of death worldwide. Neddylation is a post-translational modification involved in several processes such as cell growth, viability and development. Importantly, the neddylation pathway is upregulated in liver cancer and specifically enriched in patients with poor prognosis. Hu antigen R (HuR), is a RNA-binding protein that stabilizes target mRNAs involved in hepatocyte proliferation, differentiation and malignant transformation. And notably, HuR levels are highly representative in liver and colon cancer. A ground-breaking knowledge about HCC has been to identify that neddylation plays a role in HCC by regulating the liver oncogenic driver HuR. In addition, the neddylation inhibitor MLN4924 has shown antitumoral effects in vitro and in vivo in liver cancer, partly through HuR destabilization. Importantly, high levels of HuR made hepatoma cells more resistant to neddylation inhibition while low levels of HuR sensitized cells to the treatment, suggesting that the levels of HuR determine the druggability of the neddylation pathway in HCC. Overall, our findings highlight the impact that neddylation plays in liver cancer and open a completely new area of research, paving the way for novel therapeutical approaches.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656885","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: 1
The anti-melanoma activity and oncogenic targets of hsa-miR-15a-5p. hsa-miR-15a-5p的抗黑色素瘤活性和致癌靶点。
RNA & disease (Houston, Tex.) Pub Date : 2016-01-01 Epub Date: 2016-11-14
Christopher Alderman, Yixin Yang
{"title":"The anti-melanoma activity and oncogenic targets of hsa-miR-15a-5p.","authors":"Christopher Alderman,&nbsp;Yixin Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MiRNAs regulate gene expression post-transcriptionally and pre-translationally. Through gene regulation, several miRNAs have been found to play a significant role in various diseases. Each miRNA has multiple targets and is able to have a potent, albeit complex, effect on the cells. Specifically, miRNA-15a has been found to significantly reduce cancer cell survival and aggressiveness through multiple mechanisms across several cancer types. Our research found that miRNA-15a was able to decrease melanoma cell viability in-vitro and in-vivo. We have also found that miRNA-15a caused cell cycle arrest at the G<sub>0</sub>/G<sub>1</sub> phase. Moreover, miRNA-15a was found to decrease the invasiveness of melanoma cells. CDCA4 was also discovered as a novel <i>bona-fide</i> target of miRNA-15a. The following oncogenic mRNAs are verified targets of miRNA-15a: CDCA4, BCL2L2, YAP1, AKT-3, Cyclin E1, and γ-Synuclein. In the future we hope to better understand which miRNAs will be effective in different transcriptome and genome environments. Efforts such as the NIH Center for Cancer Genomics' 'The Cancer Genome Atlas,' 'Cancer Target and Driver Discovery Network,' and the 'Human Cancer Models Initiatives' among others, will help us characterize the specific tumor environments in which different miRNAs are able to reduce cancer proliferation and aggression. This information will be enhanced by improving the delivery of miRNA by inducing its expression in-situ with dCas9 conjugated to activation domains.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34805643","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
Functional interplay between PPM1G and the transcription elongation machinery. PPM1G与转录延伸机制之间的功能相互作用。
RNA & disease (Houston, Tex.) Pub Date : 2016-01-01 Epub Date: 2016-03-14
Swapna Aravind Gudipaty, Iván D'Orso
{"title":"Functional interplay between PPM1G and the transcription elongation machinery.","authors":"Swapna Aravind Gudipaty,&nbsp;Iván D'Orso","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transcription elongation is a critical regulatory step in the gene expression cycle. One key regulator of the switch between transcription initiation and elongation is the P-TEFb kinase, which phosphorylates RNA polymerase II (Pol II) and several negative elongation factors to relieve the elongation block at paused promoters to facilitate productive elongation. Here, we highlight recent findings signifying the role of the PPM1G/PP2Cγ phosphatase in activating and maintaining the active transcription elongation state by regulating the availability of P-TEFb and blocking its assembly into the catalytic inactive 7SK small nuclear ribonucleoprotein (snRNP) complex.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34323842","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
Antisense Oligonucleotides: Treatment Strategies and Cellular Internalization. 反义寡核苷酸：治疗策略与细胞内化。
RNA & disease (Houston, Tex.) Pub Date : 2016-01-01 Epub Date: 2016-08-15 DOI: 10.14800/rd.1393
Colton M Miller, Edward N Harris
{"title":"Antisense Oligonucleotides: Treatment Strategies and Cellular Internalization.","authors":"Colton M Miller, Edward N Harris","doi":"10.14800/rd.1393","DOIUrl":"10.14800/rd.1393","url":null,"abstract":"<p><p>The clinical applicaton of antisense oligonucleotides (ASOs) is becoming more of a reality as several drugs have been approved for the treatment of human disorders and many others are in various phases in development and clinical trials. ASOs are short DNA/RNA oligos which are heavily modified to increase their stability in biological fluids and retain the properties of creating RNA-RNA and DNA-RNA duplexes that knock-down or correct genetic expression. This review outlines several strategies that ASOs utilize for the treatment of various congenital diseases and syndromes that develop with aging. In addition, we discuss some of the mechanisms for specific non-targeted ASO internalization within cells.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376066/pdf/nihms-815547.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34883081","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
MicroRNA-based screens for synthetic lethal interactions with c-Myc. 基于 MicroRNA 筛选与 c-Myc 的合成致死相互作用。
RNA & disease (Houston, Tex.) Pub Date : 2016-01-01 Epub Date: 2016-05-30 DOI: 10.14800/rd.1330
Youjun Li, Yahui Zhu, Edward V Prochownik
{"title":"MicroRNA-based screens for synthetic lethal interactions with c-Myc.","authors":"Youjun Li, Yahui Zhu, Edward V Prochownik","doi":"10.14800/rd.1330","DOIUrl":"10.14800/rd.1330","url":null,"abstract":"<p><p>microRNAs (miRs) are small, non-coding RNAs, which play crucial roles in the development and progression of human cancer. Given that miRs are stable, easy to synthetize and readily introduced into cells, they have been viewed as having potential therapeutic benefit in cancer. c-Myc (Myc) is one of the most commonly deregulated oncogenic transcription factors and has important roles in the pathogenesis of cancer, thus making it an important, albeit elusive therapeutic target. Here we review the miRs that have been identified as being both positive and negative targets for Myc and how these participate in the complex phenotypes that arise as a result of Myc-driven transformation. We also discussseveral recent reports of Myc-synthetic lethal interactions with miRs.These highlight the importance and complexity of miRs in Myc-mediated biological functions and the opportunities for Myc-driven human cancer therapies.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"3 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657154","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
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