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microRNA biogenesis pathway

Xiao Fu, Mengjie Liu, Shengyang Qu, Jiequn Ma, Yamin Zhang, Tingting Shi, Hongqing Wen, Yujuan Yang, Shuhong Wang, Jing Wang, Kejun Nan, Yu Yao, Tao Tian
BACKGROUND: Multidrug resistance is the main obstacle for hepatocellular carcinoma (HCC) treatment. miR-32-5p is involved in HCC progression but its function in multidrug resistance is still unclear. Here we aim to find out the function of miR-32-5p in inducing multidrug resistance and its underlying mechanisms of transforming sensitive cell to resistant cell. METHODS: We detected the expression of miR-32-5p and PTEN in the multidrug-resistant cell line (Bel/5-FU) and the sensitive cell line (Bel7402), HCC and para-carcinoma liver tissues through real-time PCR...
March 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
Karen E Hayes, Jamie A Barr, Mingyi Xie, Joan A Steitz, Ivan Martinez
Cellular quiescence (also known as G0 arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27Kip1 . Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating cellular quiescence. Our recent publication demonstrated the existence of an alternative miRNA biogenesis pathway in primary human foreskin fibroblast (HFF) cells during quiescence...
February 5, 2018: Bio-protocol
Frank Curmi, Ruben J Cauchi
Gemin3, also known as DDX20 or DP103, is a DEAD-box RNA helicase which is involved in more than one cellular process. Though RNA unwinding has been determined in vitro , it is surprisingly not required for all of its activities in cellular metabolism. Gemin3 is an essential gene, present in Amoeba and Metazoa. The highly conserved N-terminus hosts the helicase core, formed of the helicase- and DEAD-domains, which, based on crystal structure determination, have key roles in RNA binding. The C-terminus of Gemin3 is highly divergent between species and serves as the interaction site for several accessory factors that could recruit Gemin3 to its target substrates and/or modulate its function...
March 9, 2018: Biochemical Society Transactions
Zhenfei Sun, Min Li, Ying Zhou, Tongtong Guo, Yin Liu, Hui Zhang, Yuda Fang
Light and microRNAs (miRNAs) are key external and internal signals for plant development, respectively. However, the relationship between the light signaling and miRNA biogenesis pathways remains unknown. Here we found that miRNA processer proteins DCL1 and HYL1 interact with a basic helix-loop-helix (bHLH) transcription factor, phytochrome-interacting factor 4 (PIF4), which mediates the destabilization of DCL1 during dark-to-red-light transition. PIF4 acts as a transcription factor for some miRNA genes and is necessary for the proper accumulation of miRNAs...
March 9, 2018: PLoS Genetics
Barbara Ogórek, Hilaire C Lam, Damir Khabibullin, Heng-Jia Liu, Julie Nijmeh, Robinson Triboulet, David J Kwiatkowski, Richard I Gregory, Elizabeth P Henske
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disease caused by germline inactivating mutations of TSC1 or TSC2. In TSC-associated tumors of the brain, heart, skin, kidney, and lung, inactivation of both alleles of TSC1 or TSC2 leads to hyperactivation of the mTORC1 pathway. The TSC/mTORC1 pathway is a key regulator of cellular processes related to growth, proliferation and autophagy. We and others have previously found that mTORC1 regulates microRNA biogenesis, but the mechanisms are not fully understood...
March 2, 2018: Human Molecular Genetics
Shubaash Anthiya, Audrey Griveau, Claire Loussouarn, Patrick Baril, Martin Garnett, Jean-Paul Issartel, Emmanuel Garcion
MicroRNAs (miRNAs) are key regulatory elements encoded by the genome. A single miRNA can downregulate the expression of multiple genes involved in diverse functions. Because cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma (GBM), this review provides an up-to-date summary of miRNA biogenesis, the role of miRNA in cancer resistance, and essential tools for modulating miRNA expression, as well as of clinically promising RNAi delivery systems and how they can be adapted for therapy...
March 2018: Trends in Cancer
Igor I Titov, Pavel S Vorozheykin
BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA. RESULTS: We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer...
February 9, 2018: BMC Genomics
Lucile Fressigné, Martin J Simard
In recent years, the discovery of small non-coding RNAs has opened an all new field in molecular biology. Indeed, these non-coding sequences give rise to powerful regulators of gene expression. Nowadays, different types of small non-coding RNAs have been described. Of these, the best-characterized types are microRNAs, piRNAs (Piwi-interacting RNAs) and siRNAs (small interfering RNAs). Because of their fine-tuning important function in the regulation of gene and genome expression, an aberrant expression level of those small non-coding RNAs are associated to several pathologies...
February 2018: Médecine Sciences: M/S
Shi-Lung Lin, Shao-Yao Ying
MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA interference (RNAi), a post-transcriptional gene-silencing mechanism. Recent evidence also indicates that they are involved in the transcriptional regulation of genome activities. They were first discovered in Caenorhabditis elegans as native RNA fragments that modulate a wide range of genetic regulatory pathways during embryonic development, and are now recognized as small gene silencers transcribed from the noncoding regions of a genome...
2018: Methods in Molecular Biology
E C Martin, A T Qureshi, C B Llamas, M E Burow, A G King, O C Lee, V Dasa, M A Freitas, J A Forsberg, E A Elster, T A Davis, J M Gimble
Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood...
February 7, 2018: Adipocyte
Randall F D'Souza, Nina Zeng, Vandre C Figueiredo, James F Markworth, Brenan R Durainayagam, Sarah M Mitchell, Aaron C Fanning, Sally D Poppitt, David Cameron-Smith, Cameron J Mitchell
Limb immobilization results in a rapid loss of muscle size and strength. The resultant alterations in signalling pathways governing myogenesis, catabolism and mitochondrial biogenesis are likely to include post-transcriptional regulation mediated by altered microRNAs (miRNAs). Given that protein ingestion exerts an anabolic action and may act as a countermeasure to mitigate muscle loss with immobilization, it is important to examine miRNA in this context. The objective of the study was therefore to characterize the vastus lateralis miRNA response to 14 days of disuse in males (45-60 years) randomized to receive supplementation with 20 g/day of dairy protein (n = 12) or isocaloric carbohydrate placebo (n = 13)...
January 29, 2018: Molecular Nutrition & Food Research
Evelyn Chukwurah, Rekha C Patel
Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis...
January 18, 2018: Scientific Reports
Xuan Jiang, Whitney L Wooderchak-Donahue, Jamie McDonald, Prajakta Ghatpande, Mai Baalbaki, Melissa Sandoval, Daniel Hart, Hilary Clay, Shaun Coughlin, Giorgio Lagna, Pinar Bayrak-Toydemir, Akiko Hata
The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-β or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-β and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages...
January 16, 2018: Science Signaling
Kazuharu Kai, Rachel L Dittmar, Subrata Sen
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression predominantly by inhibiting transcription and/or promoting degradation of target mRNAs also in addition to being involved in non-canonical mechanisms regulating transcription, translation and cell signaling processes. Extracellular secretory miRNAs, either in complex with specific proteins or encapsulated in microvesicles called exosomes, are transported between cells as means of intercellular communication. Secretory miRNAs in circulation remain functional after delivery to recipient cells, regulating target genes and their corresponding signaling pathways...
December 19, 2017: Seminars in Cell & Developmental Biology
Yong-Ju Xu, Yang Lei, Ran Li, Ling-Li Zhang, Zhi-Xue Zhao, Jing-Hao Zhao, Jing Fan, Yan Li, Hui Yang, Jing Shang, Shunyuan Xiao, Wen-Ming Wang
Ectopic expression of the Arabidopsis RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1) boosts pattern-triggered immunity leading to enhanced resistance to different pathogens in Arabidopsis and rice. However, the underlying regulatory mechanism remains largely elusive. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT, At2g21150) positively regulates RPW8.1-mediated cell death and disease resistance. Forward genetic screen identified the b3-17 mutant that exhibited less cell death and susceptibility to powdery mildew and bacterial pathogens...
2017: Frontiers in Plant Science
Xuebin Zhang, Dasuni Jayaweera, Janny L Peters, Judit Szecsi, Mohammed Bendahmane, Jeremy A Roberts, Zinnia H González-Carranza
In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport...
2017: PloS One
Mehmet E Yalvac, Jakkrit Amornvit, Cilwyn Braganza, Lei Chen, Syed-Rehan A Hussain, Kimberly M Shontz, Chrystal L Montgomery, Kevin M Flanigan, Sarah Lewis, Zarife Sahenk
BACKGROUND: Previous studies in patients with limb-girdle muscular dystrophy type 2A (LGMD2A) have suggested that calpain-3 (CAPN3) mutations result in aberrant regeneration in muscle. METHODS: To gain insight into pathogenesis of aberrant muscle regeneration in LGMD2A, we used a paradigm of cardiotoxin (CTX)-induced cycles of muscle necrosis and regeneration in the CAPN3-KO mice to simulate the early features of the dystrophic process in LGMD2A. The temporal evolution of the regeneration process was followed by assessing the oxidative state, size, and the number of metabolic fiber types at 4 and 12 weeks after last CTX injection...
December 14, 2017: Skeletal Muscle
Jaaved Mohammed, Alex S Flynt, Alexandra M Panzarino, Md Mosharrof Hussein Mondal, Matthew DeCruz, Adam Siepel, Eric C Lai
To assess miRNA evolution across the Drosophila genus, we analyzed several billion small RNA reads across 12 fruit fly species. These data permit comprehensive curation of species- and clade-specific variation in miRNA identity, abundance, and processing. Among well-conserved miRNAs, we observed unexpected cases of clade-specific variation in 5' end precision, occasional antisense loci, and putatively noncanonical loci. We also used strict criteria to identify a large set (649) of novel, evolutionarily restricted miRNAs...
December 12, 2017: Genome Research
Ting Pan, Xiuqiang Sun, Yangxuan Liu, Hui Li, Guangbin Deng, Honghui Lin, Songhu Wang
1599 novel circRNAs and 1583 heat stress-specific circRNAs were identified in Arabidopsis. Heat stress enhanced accumulation of circRNAs remarkably. Heat stress altered the sizes of circRNAs, numbers of circularized exons and alterative circularization events. A putative circRNA-mediated ceRNA networks under heat stress was established. Heat stress retards plant growth and destabilizes crop yield. The noncoding RNAs were demonstrated to be involved in plant response to heat stress. As a newly-characterized class of noncoding RNAs, circular RNAs (circRNAs) play important roles in transcriptional and post-transcriptional regulation...
February 2018: Plant Molecular Biology
Dooyoung Lee, Chanseok Shin
DROSHA is the catalytic subunit of the Microprocessor complex, which initiates microRNA (miRNA) maturation in the nucleus by recognizing and cleaving hairpin precursors embedded in primary transcripts. However, accumulating evidence suggests that not all hairpin substrates of DROSHA are associated with the generation of functional small RNAs. By targeting those hairpins, DROSHA regulates diverse aspects of RNA metabolism across the transcriptome, serves as a line of defense against the expression of potentially deleterious elements, and permits cell fate determination and differentiation...
February 1, 2018: RNA Biology
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