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Control of Fur synthesis by the non-coding rna RyhB and iron-responsive decoding

EMBO JOUrnaL 2007年第4期26卷 965-975页

作者： Vecerek, Branislav Moll, Isabella Blaesi, Udo Univ Vienna Dept Immunol & Microbiol Max F Perutz Labs A-1030 Vienna Austria

The Fe2+-dependent Fur protein serves as a negative regulator of iron uptake in bacteria. As only metallo-Fur acts as an autogeneous repressor, Fe2+ scarcity would direct fur expression when continued supply is not obviously required. We show that in Escherichia coli post-transcriptional regulatory mechanisms ensure that Fur synthesis remains steady in iron limitation. Our studies revealed that fur translation is coupled to that of an upstream open reading frame (uof), translation of which is downregulated by the non-coding rna (ncrna) RyhB. As RyhB transcription is negatively controlled by metallo-Fur, iron depletion creates a negative feedback loop. RyhB-mediated regulation of uof-fur provides the first example for indirect translational regulation by a trans-encoded ncrna. In addition, we present evidence for an iron-responsive decoding mechanism of the uof-fur entity. It could serve as a backup mechanism of the RyhB circuitry, and represents the first link between iron availability and synthesis of an iron-containing protein.

关键词： fur iron MiaB non-coding rna RyhB

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UV Irradiation Induces a non-coding rna that Functionally Opposes the Protein Encoded by the Same Gene

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CELL 2017年第5期168卷 843-+页

作者： Williamson, Laura Saponaro, Marco Boeing, Stefan East, Philip Mitter, Richard Kantidakis, Theodoros Kelly, Gavin P. Lobley, Anna Walker, Jane Spencer-Dene, Bradley Howell, Michael Stewart, Aengus Svejstrup, Jesper Q. Francis Crick Inst Clare Hall Labs Mech Transcript Lab S Mimms EN6 3LD Herts England Univ Birmingham Inst Canc & Genom Sci Vincent Dr Birmingham B15 2TT W Midlands England Francis Crick Inst Bioinformat & Biostat 1 Midland Rd London NW1 1AT England Francis Crick Inst Expt Histopathol 1 Midland Rd London NW1 1AT England Francis Crick Inst High Throughput Screening Lab 1 Midland Rd London NW1 1AT England

The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slow-down of transcript elongation and restriction of gene activity to the promoter-proximal similar to 25 kb is observed. This is associated with a shift from expression of long mrnas to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mrna to a shorter ALE isoform of which the rna, rather than an encoded protein, is critical for the eventual recovery of transcription. The non-coding ASCC3 isoform counteracts the function of the protein-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and non-coding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage.

关键词： DNA damage response transcript elongation ASCC3 non-coding rna lncrna alternative last exon splicing UV-irradiation rna polymerase II

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Deciphering the Role of Exosomal non-coding rna (ncrna) in Drug Resistance of Gastrointestinal Tumors;an Updated Review

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CELL BIOCHEMISTRY AND BIOPHYSICS 2024年第2期82卷 609-621页

作者： Tashakori, Nafiseh Armanfar, Maryam Mashhadi, Anahita Mohammed, Adil Tawfeeq Karim, Manal Morad Hussein, Abbas Hameed Abdul Adil, Mohaned Azimi, Sajad Ataei Abedini, Fatemeh Islamic Azad Univ Fac Internal Med Dept Med Tehran Branch Tehran Iran Univ Shahid Beheshti Med Sci Fac Internal Med Dept Internal Med Tehran Iran Islamic Azad Univ Dept Med Lab Sci Arak branch Arak Iran Al Noor Univ Coll Nineveh Iraq Natl Univ Sci & Technol Coll Pharm Dhi Qar 64001 Iraq Ahl Al Bayt Univ Kerbala Iraq Al Farahidi Univ Pharm Coll Baghdad Iraq Mashhad Univ Med Sci Hematol Oncol Mashhad Iran Sci & Art Univ Dept Biol Yazd Iran

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding rnas, like micrornas and long non-coding rnas (lncrnas), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding rnas (ncrnas). Therefore, it should come as a wonder that several ncrnas have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncrnas often act as a competitive endogenous rna (cerna) of mirnas to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncrna-enriched exosomes in GI medication resistance.

关键词： non-coding rna Cancer GI cancer Drug resistance Exosome

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Comprehensive long non-coding rna expression profiling reveals their potential roles in systemic lupus erythematosus

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CELLULAR IMMUNOLOGY 2017年 319卷 17-27页

作者： Li, Lian-Ju Zhao, Wei Tao, Sha-Sha Li, Jun Xu, Shu-Zhen Wang, Jie-Bing Leng, Rui-Xue Fan, Yin-Guang Pan, Hai-Feng Ye, Dong-Qing Anhui Med Univ Sch Publ Hlth Dept Epidemiol & Biostat 81 Meishan Rd Hefei 230032 Anhui Peoples R China Anhui Prov Key Lab Major Autoimmune Dis Hefei Anhui Peoples R China

Long non-coding rnas can regulate gene transcription, modulate protein function, and act as competing endogenous rna. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncrnas in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncrnas and 1977 mrnas were differentially expressed. QRT-PCR showed downregulated uc001ykl. 1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncrnas whose expressions might correlate with disease activity of SLE patients. coding-non-coding gene coexpression analyses showed differential lncrnas might operate via modulating expressions of their correlated, relevant mrnas in SLE. Differential lncrnas might also function through their cernas. Our study established that the aberrant expression profiles of lncrnas may play a role in SLE and thus warrant further investigation.

关键词： Long non-coding rna Systemic lupus erythematosus non-coding rna Microrna cerna

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Deep sequencing of coding and non-coding rna in the CNS

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BRAIN RESEARCH 2010年 1338卷 146-154页

作者： van der Brug, Marcel Nalls, Michael A. Cookson, Mark R. NIA Cell Biol & Gene Express Unit Neurogenet Lab Bethesda MD 20892 USA Scripps Res Inst Dept Neurosci Jupiter FL 33458 USA

Several methods now exist for identifying and quantifying many biological events in parallel and in a relatively unbiased fashion. For gene expression experiments, cloning approaches have been supplemented with microarray platforms over the past few years. The focus of this review is on deep sequencing, a new set of techniques that can be used to both identify rna species and quantify them in a massively parallel fashion. Deep sequencing has some advantages over other methods, driven largely by the high depth of coverage for any library of nucleic acids. This allows, for example, estimates of alternative splicing and untranslated region utilization. We will discuss how deep sequencing methods are being applied to characterization of gene expression in the brain and how these technologies might develop over the next few years. Published by Elsevier B.V.

关键词： Alternative splicing Deep sequencing Gene expression Massively parallel signature sequencing Next generation sequencing non-coding rna Small rna

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"Hypothesis for the Modern rna World": A pervasive non-coding rna-Based Genetic Regulation is a Prerequisite for the Emergence of Multicellular Complexity

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ORIGINS OF LIFE AND EVOLUTION OF BIOSPHERES 2011年第6期41卷 587-607页

作者： Lozada-Chavez, Irma Stadler, Peter F. Prohaska, Sonja J. Univ Leipzig Computat EvoDevo Grp D-04107 Leipzig Germany Univ Leipzig Bioinformat Grp Dept Comp Sci D-04107 Leipzig Germany Univ Leipzig Interdisciplinary Ctr Bioinformat D-04107 Leipzig Germany Max Planck Inst Math Sci D-04103 Leipzig Germany Fraunhofer Inst Zelltherapie & Immunol IZI D-04103 Leipzig Germany Univ Vienna Dept Theoret Chem A-1090 Vienna Austria Univ Copenhagen Ctr Noncoding RNA Technol & Hlth DK-1870 Frederiksberg C Denmark Santa Fe Inst Santa Fe NM 87501 USA

The transitions to multicellularity mark the most pivotal and distinctive events in life's history on Earth. Although several transitions to "simple" multicellularity (SM) have been recorded in both bacterial and eukaryotic clades, transitions to complex multicellularity (CM) have only happened a few times in eukaryotes. A large number of cell types (associated with large body size), increased energy consumption per gene expressed, and an increment of non-protein-coding DNA positively correlate with CM. These three factors can indeed be understood as the causes and consequences of the regulation of gene expression. Here, we discuss how a vast expansion of non-protein-coding rna (ncrnas) regulators rather than large numbers of novel protein regulators can easily contribute to the emergence of CM. We also propose that the evolutionary advantage of rna-based gene regulation derives from the robustness of the rna structure that makes it easy to combine genetic drift with functional exploration. We describe a model which aims to explain how the evolutionary dynamic of ncrnas becomes dominated by the accessibility of advantageous mutations to innovate regulation in complex multicellular organisms. The information and models discussed here outline the hypothesis that pervasive ncrna-based regulatory systems, only capable of being expanded and explored in higher eukaryotes, are prerequisite to complex multicellularity. Thereby, regulatory rna molecules in Eukarya have allowed intensification of morphological complexity by stabilizing critical phenotypes and controlling developmental precision. Although the origin of rna on early Earth is still controversial, it is becoming clear that once rna emerged into a protocellular system, its relevance within the evolution of biological systems has been greater than we previously thought.

关键词： Modern rna world Multicellular complexity Eukaryote evolution Genome complexity non-coding rna Gene regulation

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Role of microrna and long non-coding rna in Marek's disease tumorigenesis in chicken

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RESEARCH IN VETERINARY SCIENCE 2021年 135卷 134-142页

作者： Zhang, Zhaobo Zhang, Sishi Wang, Guoshuai Feng, Siyu Han, Kexin Han, Limei Han, Liping Shenyang Agr Univ Coll Anim Sci & Vet Med Key Lab Livestock Infect Dis Northeast China Minist Educ Shenyang 110866 Peoples R China Chinese Acad Agr Sci Shanghai Vet Res Inst Shanghai 200241 Peoples R China Changchun Normal Univ Dept Biosci Changchun 130032 Peoples R China

Marek?s disease virus (MDV), the causative agent of Marek?s disease (MD), results in highly infectious phymatosis, lymphatic tissue hyperplasia, and neoplasia. MD is associated with high morbidity and mortality rate. noncoding rnas (ncrnas) entails long non-coding rna (lncrna) and microrna (mirna). Numerous studies have reported that specific mirnas and lncrnas participate in multiple cellular processes, such as proliferation, migration, and tumor cell invasion. Specialized mirnas and lncrnas militate a similar role in MD tumor oncogenesis. Despite its growing popularity, only a few reviews are available on ncrna in MDV tumor oncogenes. Herein, we summarized the role of the mirnas and lncrnas in MD tumorigenesis. Altogether, we brought forth the research issues, such as MD prevention, screening, regulatory network formation, novel mirnas, and lncrnas analysis in MD that needs to be explored further. This review provides a theoretical platform for the further analysis of mirnas and lncrnas functions and the prevention and control of MD and malignancies in domestic animals.

关键词： non-coding rna microrna Long non-coding rna Tumorigenesis Chicken

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Prognostic values of the immune microenvironment-related non-coding rna IGF2BP2-AS1 in bladder cancer

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CELL CYCLE 2022年第23期21卷 2533-2549页

作者： Ding, Ke Zheng, Zhihuan Han, Yu Huang, Xiangyun Cent South Univ Xiangya Hosp Dept Urol Changsha Peoples R China Cent South Univ Xiangya Hosp 2 Dept Anesthesiol Changsha 412008 Hunan Peoples R China

Bladder cancer can range from noninvasive to invasive tumors. When non-muscle invasive bladder cancer (NMIBC) recurs, patients could endure long-term invasive malignancies with a high disease-specific death rate. Immune escape frequently results in tumor development, metastases, unfavorable prognosis, and failure of immunotherapy. Based on the median immune score, this study used ESTIMATE scores to evaluate 411 bladder cancer cases from TCGA-BLCA. Two hundred two ncrnas were differentially expressed in two groups, where 29 candidates appeared to be associated with the overall survival of bladder cancer patients. LASSO algorithm was performed to establish the risk score model of 13-ncrna. Risk scores were computed for cases in the training set, validation set, and TCGA-BLCA set;Poor prognosis in cases with higher risk scores was based on the training set, validating set, and TCGA-BLCA set. Among the 13 ncrnas, IGF2BP2-AS1, MAGF-AS1, ARHGAP5-AS1, and LINC00942 were significantly correlated with the overall survival of bladder cancer patients. Pearson's correlation analysis based on TCGA-BLCA identified 2093, 3107, 386, and 936 mrnas co-expressed with IGF2BP2-AS1, MAGF-AS1, ARHGAP5-AS1, and LINC00942, respectively. Conclusively, the 13 ncrna signature exhibited a feasible predictive prognostic value for bladder cancer patients. IGF2BP2-AS1 expression was higher in bladder cancer tissues and significantly correlated to immune-related factors, suggesting that IGF2BP2-AS1 represents a promising immune-related target for treating bladder cancer patients.

关键词： Bladder cancer ESTIMATE algorithm LASSO algorithm non-coding rna IGF2BP2-AS1

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SHARAKU: an algorithm for aligning and clustering read mapping profiles of deep sequencing in non-coding rna processing

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BIOINFORMATICS 2016年第12期32卷 369-377页

作者： Tsuchiya, Mariko Amano, Kojiro Abe, Masaya Seki, Misato Hase, Sumitaka Sato, Kengo Sakakibara, Yasubumi Keio Univ Dept Biosci & Informat Yokohama Kanagawa 1610031 Japan

Motivation: Deep sequencing of the transcripts of regulatory non-coding rna generates footprints of post-transcriptional processes. After obtaining sequence reads, the short reads are mapped to a reference genome, and specific mapping patterns can be detected called read mapping profiles, which are distinct from random non-functional degradation patterns. These patterns reflect the maturation processes that lead to the production of shorter rna sequences. Recent nextgeneration sequencing studies have revealed not only the typical maturation process of mirnas but also the various processing mechanisms of small rnas derived from trnas and snornas. Results: We developed an algorithm termed SHARAKU to align two read mapping profiles of nextgeneration sequencing outputs for non-coding rnas. In contrast with previous work, SHARAKU incorporates the primary and secondary sequence structures into an alignment of read mapping profiles to allow for the detection of common processing patterns. Using a benchmark simulated dataset, SHARAKU exhibited superior performance to previous methods for correctly clustering the read mapping profiles with respect to 50-end processing and 30-end processing from degradation patterns and in detecting similar processing patterns in deriving the shorter rnas. Further, using experimental data of small rna sequencing for the common marmoset brain, SHARAKU succeeded in identifying the significant clusters of read mapping profiles for similar processing patterns of small derived rna families expressed in the brain. Availability and Implementation: The source code of our program SHARAKU is available at http://***/sharaku/, and the simulated dataset used in this work is available at the same link. Accession code: The sequence data from the whole rna transcripts in the hippocampus of the left brain used in this work is available from the DNA DataBank of Japan (DDBJ) Sequence Read Archive (DRA) under the accession number DRA004502.

关键词： non-coding rna RESEARCH rna-seq MESSENGER rna GENE mapping -- Research TRANSFER rna

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HIF-1α regulation in mammalian hibernators: role of non-coding rna in HIF-1α control during torpor in ground squirrels and bats

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JOUrnaL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY 2012年第6期182卷 849-859页

作者： Maistrovski, Yulia Biggar, Kyle K. Storey, Kenneth B. Carleton Univ Dept Biol Inst Biochem Ottawa ON K1S 5B6 Canada

A potential role for non-coding rnas, miR-106b and antisense hypoxia inducible transcription factor-1 (HIF-1 alpha), in HIF-1 alpha regulation during mammalian hibernation was investigated in two species, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and the little brown bat (Myotis lucifugus). Both species showed differential regulation of HIF-1 alpha during hibernation. HIF-1 alpha protein levels increased significantly in skeletal muscle of both species when animals entered torpor, as well as in bat liver. HIF-1 alpha mrna levels correlated with the protein increase in bat skeletal muscle and liver but not in squirrel skeletal muscle. Antisense HIF-1 alpha transcripts were identified in skeletal muscle of both hibernators. The expression of antisense HIF-1 alpha was reduced in skeletal muscle of torpid bats compared with euthermic controls, suggesting that release of inhibition by the antisense rna contributes to regulating HIF-1 alpha translation in this tissue during torpor. The expression of miR-106b, a microrna associated with HIF-1 alpha regulation, also decreased during torpor in both skeletal muscle and liver of bats and in ground squirrel skeletal muscle. These data present the first evidence that non-coding rna provides novel post-transcriptional mechanisms of HIF-1 alpha regulation when hibernators descend into deep cold torpor, and also demonstrate that these mechanisms are conserved in two divergent mammalian orders (Rodentia and Chiroptera).

关键词： Hypoxia response HIF-1 alpha Antisense rna non-coding rna Microrna Hibernation

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