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microRNA biogenesis

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https://www.readbyqxmd.com/read/28334969/a-single-mir390-targeting-event-is-sufficient-for-triggering-tas3-tasirna-biogenesis-in-arabidopsis
#1
Felipe Fenselau de Felippes, Antonin Marchais, Alexis Sarazin, Stefan Oberlin, Olivier Voinnet
In plants, tasiRNAs form a class of endogenous secondary siRNAs produced through the action of RNA-DEPENDENT-RNA-POLYMERASE-6 (RDR6) upon microRNA-mediated cleavage of non-coding TAS RNAs. In Arabidopsis thaliana, TAS1, TAS2 and TAS4 tasiRNA production proceeds via a single cleavage event mediated by 22nt-long or/and asymmetric miRNAs in an ARGONAUTE-1 (AGO1)-dependent manner. By contrast, tasiRNA production from TAS3 seems to follow the so-called 'two-hit' process, where dual targeting of TAS3, specifically mediated by the 21nt-long, symmetric miR390, initiates AGO7-dependent tasiRNA production...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330621/synergic-functions-of-mirnas-determine-neuronal-fate-of-adult-neural-stem-cells
#2
Meritxell Pons-Espinal, Emanuela de Luca, Matteo Jacopo Marzi, Ruth Beckervordersandforth, Andrea Armirotti, Francesco Nicassio, Klaus Fabel, Gerd Kempermann, Davide De Pietri Tonelli
Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs) are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs) has been unclear. As entry point to address that question we chose DICER, an endoribonuclease essential for miRNA biogenesis and other RNAi-related processes. By specific ablation of Dicer in aNSCs in vivo and in vitro, we demonstrate that miRNAs are required for the generation of new neurons, but not astrocytes, in the adult murine hippocampus...
March 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28319071/xrn2-promotes-emt-and-metastasis-through-regulating-maturation-of-mir-10a
#3
H Zhang, Y Lu, E Chen, X Li, B Lv, H G Vikis, P Liu
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28300636/perinatal-protein-malnutrition-alters-expression-of-mirna-biogenesis-genes-xpo5-and-ago2-in-mice-brain
#4
Bruno G Berardino, Estefanía A Fesser, Eduardo T Cánepa
Due to its widespread incidence, maternal malnutrition remains one of the major non-genetic factors affecting the development of newborn's brain. While all nutrients have certain influence on brain maturation, proteins appear to be the most critical for the development of neurological functions. An increasing number of studies point out that the effects of early-life nutritional inadequacy has long lasting effects on the brain and lead to permanent deficits in learning and behavior. Epigenetic mechanisms provide a potential link between the nutrition status during critical periods and changes in gene expression that may lead to disease phenotypes...
March 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28294076/microrna-biogenesis-in-hypoxia
#5
Veronika Bandara, Michael Zenon Michael, Jonathan Mark Gleadle
MicroRNAs (miRNAs) are 17-22 nucleotide, non-coding, single stranded RNA molecules that play a key role in post-transcriptional gene regulation. Hypoxia is a reduction in the normal level of tissue oxygen (O2) tension, and is a feature of chronic vascular disease, pulmonary disease and many cancers. Tissue hypoxia can have widespread effects on cellular functions, as O2 availability is critical for many cellular processes. Cells respond to changes in O2 tension through multiple molecular and cellular mechanisms, including changes in gene expression through transcriptional and translational mechanisms...
March 13, 2017: MicroRNA
https://www.readbyqxmd.com/read/28289518/role-of-micrornas-in-translation-regulation-and-cancer
#6
REVIEW
Stefania Oliveto, Marilena Mancino, Nicola Manfrini, Stefano Biffo
MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation...
February 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28287718/regulating-mirna-21-biogenesis-by-bi-functional-small-molecules
#7
Hao Yan, Umesh Bhattarai, Zhi-Fo Guo, Fu-Sen Liang
MicroRNAs (miRNAs) are non-coding RNAs that regulate translation by targeting mRNAs. In their biogenesis, precursor miRNAs (pre-miRNAs) are cleaved by RNase Dicer to give mature miRNAs. Herein, we report a new strategy to regulate miRNA biogenesis by using bi-functional small molecules that block Dicer catalyzed pre-miRNA cleavage. The bi-functional molecules consist of a pre-miRNA binding unit connected by a linker to a Dicer inhibiting unit. Recognition of a target pre-miRNA by the RNA binding unit brings the Dicer inhibitor unit into close proximity to the pre-miRNA cleavage site where it inhibits Dicer...
March 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28283057/super-enhancer-mediated-rna-processing-revealed-by-integrative-microrna-network-analysis
#8
Hiroshi I Suzuki, Richard A Young, Phillip A Sharp
Super-enhancers are an emerging subclass of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here, we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA (pri-miRNA) processing. Super-enhancers, together with broad H3K4me3 domains, shape a tissue-specific and evolutionarily conserved atlas of miRNA expression and function...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28280737/bioinformatics-study-of-structural-patterns-in-plant-microrna-precursors
#9
J Miskiewicz, K Tomczyk, A Mickiewicz, J Sarzynska, M Szachniuk
According to the RNA world theory, RNAs which stored genetic information and catalyzed chemical reactions had their contribution in the formation of current living organisms. In recent years, researchers studied this molecule diversity, i.a. focusing on small non-coding regulatory RNAs. Among them, of particular interest is evolutionarily ancient, 19-24 nt molecule of microRNA (miRNA). It has been already recognized as a regulator of gene expression in eukaryotes. In plants, miRNA plays a key role in the response to stress conditions and it participates in the process of growth and development...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28277752/regulation-of-embryonic-stem-cell-self-renewal-and-differentiation-by-micrornas
#10
Xi Ran, Chun-Hong Xiao, Gui-Ming Xiang, Xin-Ze Ran
MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. They play an important role in various cellular processes such as apoptosis, differentiation, secretion, and proliferation. Embryonic stem cells (ESCs) are derived from the inner cell mass of the blastocyst stage of the embryo. miRNAs are critical factors for the self-renewal and differentiation of ESCs. In this review, we will focus on the role of miRNAs in the self-renewal and directional differentiation of ESCs. We will present the current knowledge on key points related to miRNA biogenesis and their function in ESCs...
March 9, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28277607/identification-of-a-functional-polymorphism-affecting-microrna-binding-in-the-susceptibility-locus-1q25-3-for-colorectal-cancer
#11
Juntao Ke, Jianbo Tian, Jiaoyuan Li, Yajie Gong, Yang Yang, Ying Zhu, Yi Zhang, Rong Zhong, Jiang Chang, Jing Gong
Genome-wide association studies (GWASs) have identified dozens of susceptibility loci for colorectal cancer (CRC). However, most of them lack functional genetic variants and clear biological mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs involved in a variety of physiological and tumorigenic processes. Here we hypothesized that single nucleotide polymorphisms (SNPs) that affect miRNAs biogenesis and binding, could contribute to CRC risk in the Chinese population. To locate miRNA-related SNPs in established GWAS loci, we initially screened out five candidate SNPs using a systematic bioinformatics analysis...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28271607/dissecting-microrna-dysregulation-in-age-related-macular-degeneration-new-targets-for-eye-gene-therapy
#12
REVIEW
Anne Louise Askou, Sidsel Alsing, Andreas Holmgaard, Toke Bek, Thomas J Corydon
MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells...
March 7, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28266707/the-agotrons-gene-regulators-or-argonaute-protectors
#13
REVIEW
Lotte V W Stagsted, Iben Daugaard, Thomas B Hansen
Over the last decades, it has become evident that highly complex networks of regulators govern post-transcriptional regulation of gene expression. A novel class of Argonaute (Ago)-associated RNA molecules, the agotrons, was recently shown to function in a Drosha- and Dicer-independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as ∼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non-promiscuous miRNA-like regulators with reduced off-targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago-proteins from degradation...
March 7, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28259385/kshv-micrornas-tricks-of-the-devil
#14
REVIEW
Jie Qin, Wan Li, Shou-Jiang Gao, Chun Lu
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a vascular tumor frequently found in immunodeficient individuals. KSHV encodes 12 pre-microRNAs (pre-miRNAs), which are processed into 25 mature microRNAs (miRNAs). KSHV miRNAs maintain KSHV latency, enhance angiogenesis and dissemination of the infected cells, and interfere with the host immune system by regulating viral and cellular gene expression, ultimately contributing to KS development. In this review, we briefly introduce the biogenesis of miRNAs and then describe the recent advances in defining the roles and mechanisms of action of KSHV miRNAs in KS development...
March 2, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28257521/exosome-secretion-affects-social-motility-in-trypanosoma-brucei
#15
Dror Eliaz, Sriram Kannan, Hadassa Shaked, Gil Arvatz, Itai Dov Tkacz, Lior Binder, Hiba Waldman Ben-Asher, Uthman Okalang, Vaibhav Chikne, Smadar Cohen-Chalamish, Shulamit Michaeli
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28252644/nuclear-drosha-enhances-cell-invasion-via-an-egfr-erk1-2-mmp7-signaling-pathway-induced-by-dysregulated-mirna-622-197-and-their-targets-lamc2-and-cd82-in-gastric-cancer
#16
Liyun Xu, Yixuan Hou, Gang Tu, Yanlin Chen, Yan-E Du, Hailong Zhang, Siyang Wen, Xi Tang, Jiali Yin, Lei Lang, Kexin Sun, Guanglun Yang, Xiaoli Tang, Manran Liu
Drosha is an RNA III-like enzyme that has an aberrant expression in some tumors. Our previous studies showed the aberrant Drosha in gastric tumors. However, the roles of nuclear Drosha, the main regulator of microRNA (miRNA) biogenesis, in gastric cancer (GC) progression remain poorly understood. In this study, we demonstrated that nuclear Drosha is significantly associated with cell invasion of GC and that Drosha silence impedes the tumor invasion. Knockdown of Drosha led to a set of dysregulated miRNAs in GC cells...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28244490/the-rna-binding-protein-qki5-regulates-primary-mir-124-1-processing-via-a-distal-rna-motif-during-erythropoiesis
#17
Fang Wang, Wei Song, Hongmei Zhao, Yanni Ma, Yuxia Li, Di Zhai, Jingnan Pi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui, Linfang Wang, Jia Yu
MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation...
March 2017: Cell Research
https://www.readbyqxmd.com/read/28238105/emerging-role-of-micrornas-in-mtor-signaling
#18
REVIEW
Yanjie Zhang, Bo Huang, Hui-Yun Wang, Augustus Chang, X F Steven Zheng
Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a critical role in the control of cellular growth and metabolism. Hyperactivation of mTOR pathway is common in human cancers, driving uncontrolled proliferation. MicroRNA (miRNA) is a class of short noncoding RNAs that regulate the expression of a wide variety of genes. Deregulation of miRNAs is a hallmark of cancer. Recent studies have revealed interplays between miRNAs and the mTOR pathway during cancer development. Such interactions appear to provide a fine-tuning of various cellular functions and contribute qualitatively to the behavior of cancer...
February 25, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28236575/unravelling-endogenous-microrna-system-dysfunction-as-a-new-pathophysiological-mechanism-in-machado-joseph-disease
#19
Vitor Carmona, Janete Cunha-Santos, Isabel Onofre, Ana Teresa Simões, Udaya Vijayakumar, Beverly L Davidson, Luís Pereira de Almeida
Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3' UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3' UTR and whether they can alleviate MJD neuropathology in vivo...
February 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28229250/role-of-mirnas-in-human-disease-and-inborn-errors-of-metabolism
#20
Ana Rivera-Barahona, Belén Pérez, Eva Richard, Lourdes R Desviat
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression posttranscriptionally by base pairing with target messenger RNAs (mRNAs). They are estimated to target ∼60% of all human protein-coding genes and are involved in regulating key physiological processes and intracellular signaling pathways. They also exhibit tissue specificity, and their dysregulation is linked to the progression of pathology. Identifying disease associated miRNAs and their respective targets provides novel molecular insight into disease, enabling the design of new therapeutic strategies...
February 22, 2017: Journal of Inherited Metabolic Disease
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