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https://www.readbyqxmd.com/read/29765864/non-canonical-post-transcriptional-rna-regulation-of-neural-stem-cell-potential
#1
REVIEW
Chiara Rolando, Verdon Taylor
Adult brain structures and complexity emerge from a single layer of neuroepithelial cells that early during the development give rise to neural stem cells (NSCs). NSCs persist in restricted regions of the postnatal brain where they support neurogenesis throughout life thus allowing brain plasticity and adaptation. NSC regulation involves a precise coordination of intrinsic and extrinsic mechanisms that finely modulate the neurogenic process. Here we will discuss new mechanisms of post-transcriptional gene regulation that act in the embryonic and adult brain to regulate NSC maintenance and differentiation...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29765080/distinguishing-mirtrons-from-canonical-mirnas-with-data-exploration-and-machine-learning-methods
#2
Grzegorz Rorbach, Olgierd Unold, Bogumil M Konopka
Mirtrons are non-canonical microRNAs encoded in introns the biogenesis of which starts with splicing. They are not processed by Drosha and enter the canonical pathway at the Exportin-5 level. Mirtrons are much less evolutionary conserved than canonical miRNAs. Due to the differences, canonical miRNA predictors are not applicable to mirtron prediction. Identification of differences is important for designing mirtron prediction algorithms and may help to improve the understanding of mirtron functioning. So far, only simple, single-feature comparisons were reported...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760646/dgcr8-promotes-neural-progenitor-expansion-and-represses-neurogenesis-in-the-mouse-embryonic-neocortex
#3
Nadin Hoffmann, Stefan C Weise, Federica Marinaro, Tanja Vogel, Davide De Pietri Tonelli
DGCR8 and DROSHA are the minimal functional core of the Microprocessor complex essential for biogenesis of canonical microRNAs and for the processing of other RNAs. Conditional deletion of Dgcr8 and Drosha in the murine telencephalon indicated that these proteins exert crucial functions in corticogenesis. The identification of mechanisms of DGCR8- or DROSHA-dependent regulation of gene expression in conditional knockout mice are often complicated by massive apoptosis. Here, to investigate DGCR8 functions on amplification/differentiation of neural progenitors cells (NPCs) in corticogenesis, we overexpress Dgcr8 in the mouse telencephalon, by in utero electroporation ( IU Ep)...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29750274/microprocessor-depends-on-hemin-to-recognize-the-apical-loop-of-primary-microrna
#4
Tuan Anh Nguyen, Joha Park, Thi Lieu Dang, Yeon-Gil Choi, V Narry Kim
Microprocessor, which consists of a ribonuclease III DROSHA and its cofactor DGCR8, initiates microRNA (miRNA) maturation by cleaving primary miRNA transcripts (pri-miRNAs). We recently demonstrated that the DGCR8 dimer recognizes the apical elements of pri-miRNAs, including the UGU motif, to accurately locate and orient Microprocessor on pri-miRNAs. However, the mechanism underlying the selective RNA binding remains unknown. In this study, we find that hemin, a ferric ion-containing porphyrin, enhances the specific interaction between the apical UGU motif and the DGCR8 dimer, allowing Microprocessor to achieve high efficiency and fidelity of pri-miRNA processing in vitro...
May 10, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29746670/dicer-cleaves-5-extended-microrna-precursors-originating-from-rna-polymerase-ii-transcription-start-sites
#5
Peike Sheng, Christopher Fields, Kelsey Aadland, Tianqi Wei, Oralia Kolaczkowski, Tongjun Gu, Bryan Kolaczkowski, Mingyi Xie
MicroRNAs (miRNAs) are approximately 22 nucleotide (nt) long and play important roles in post-transcriptional regulation in both plants and animals. In animals, precursor (pre-) miRNAs are ∼70 nt hairpins produced by Drosha cleavage of long primary (pri-) miRNAs in the nucleus. Exportin-5 (XPO5) transports pre-miRNAs into the cytoplasm for Dicer processing. Alternatively, pre-miRNAs containing a 5' 7-methylguanine (m7G-) cap can be generated independently of Drosha and XPO5. Here we identify a class of m7G-capped pre-miRNAs with 5' extensions up to 39 nt long...
May 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29723684/the-role-of-exportin-5-in-microrna-biogenesis-and-cancer
#6
REVIEW
Ke Wu, Juan He, Wenchen Pu, Yong Peng
MicroRNAs (miRNAs) are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs (pre-miRNAs) from the nucleus to the cytoplasm by exportin-5 (XPO5). Given the critical role of nuclear export of pre-miRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis...
April 30, 2018: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/29717063/nuclear-pten-enhances-the-maturation-of-a-microrna-regulon-to-limit-myd88-dependent-susceptibility-to-sepsis
#7
Flavia Sisti, Soujuan Wang, Stephanie L Brandt, Nicole Glosson-Byers, Lindsey D Mayo, Young Min Son, Sarah Sturgeon, Luciano Filgueiras, Sonia Jancar, Hector Wong, Charles S Dela Cruz, Nathaniel Andrews, Jose Carlos Alves-Filho, Fernando Q Cunha, C Henrique Serezani
Sepsis-induced organ damage is caused by systemic inflammatory response syndrome (SIRS), which results in substantial comorbidities. Therefore, it is of medical importance to identify molecular brakes that can be exploited to dampen inflammation and prevent the development of SIRS. We investigated the role of phosphatase and tensin homolog (PTEN) in suppressing SIRS, increasing microbial clearance, and preventing lung damage. Septic patients and mice with sepsis exhibited increased PTEN expression in leukocytes...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29627294/%C3%AE-arrestin-biased-agonism-of-%C3%AE-adrenergic-receptor-regulates-dicer-mediated-microrna-maturation-to-promote-cardioprotective-signaling
#8
Jian-Peng Teoh, Ahmed S Bayoumi, Tatsuya Aonuma, Yanyan Xu, John A Johnson, Huabo Su, Neal L Weintraub, Yaoliang Tang, Il-Man Kim
RATIONALE: MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate target genes. First transcribed as primary miR transcripts (pri-miRs), they are enzymatically processed by Drosha into premature miRs (pre-miRs) and further cleaved by Dicer into mature miRs. Initially discovered to desensitize β-adrenergic receptor (βAR) signaling, β-arrestins are now well-appreciated to modulate multiple pathways independent of G protein signaling, a concept known as biased signaling...
April 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29615481/srsf3-recruits-drosha-to-the-basal-junction-of-primary-micrornas
#9
Kijun Kim, Trung Duc Nguyen, Shaohua Li, Tuan Anh Nguyen
The Microprocessor complex, consisting of an RNase III DROSHA and the DGCR8 dimer, cleaves primary microRNA transcripts (pri-miRNAs) to initiate microRNA (miRNA) maturation. Pri-miRNAs are stem-loop RNAs, and ~79% of them contain at least one of the three major and conserved RNA motifs, UG, UGU, and CNNC. We recently demonstrated that the basal UG and apical UGU motifs of pri-miRNAs interact with DROSHA and DGCR8, respectively. They help orient Microprocessor on the pri-miRNA in a proper direction in which DROSHA and DGCR8 localize to the basal and apical pri-miRNA junctions, respectively...
April 3, 2018: RNA
https://www.readbyqxmd.com/read/29600985/role-of-components-of-microrna-machinery-in-carcinogenesis
#10
R Kian, S Moradi, S Ghorbian
MicroRNAs (miRNAs) are a broad class of non-coding RNAs nearly 21 nucleotides length, which play crucial functions in post-transcriptional gene regulation. These molecules are associated with many developmental and cellular processes in eukaryotic organisms. Current investigation has reported major factors contributing to miRNA biogenesis and has constituted basic principles of miRNA function. More recently, it was confirmed that various miRNAs are clearly implicated in human malignancies, such as lung, breast, ovarian, bladder, colon cancer and other kinds of carcinoma...
March 2018: Experimental Oncology
https://www.readbyqxmd.com/read/29573145/profiling-of-m6a-rna-modifications-identified-an-age-associated-regulation-of-ago2-mrna-stability
#11
Kyung-Won Min, Richard W Zealy, Sylvia Davila, Mikhail Fomin, James C Cummings, Daniel Makowsky, Catherine H Mcdowell, Haley Thigpen, Markus Hafner, Sang-Ho Kwon, Constantin Georgescu, Jonathan D Wren, Je-Hyun Yoon
Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the regulatory steps in transcription, post-transcription, and post-translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6-methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells (PBMCs) from young and old cohorts...
March 23, 2018: Aging Cell
https://www.readbyqxmd.com/read/29545743/lrrk2-contributes-to-secondary-brain-injury-through-a-p38-drosha-signaling-pathway-after-traumatic-brain-injury-in-rats
#12
Qin Rui, Haibo Ni, Fan Gao, Baoqi Dang, Di Li, Rong Gao, Gang Chen
Leucine-rich repeat kinase 2 (LRRK2) is widely expressed in the brain and exerts neurotoxicity in Parkinson's disease. The p38/Drosha signaling activation has been reported to increase cell death under stress. This study was designed to investigate the potential role and mechanism of LRRK2 in secondary brain injury after traumatic brain injury (TBI). A total of 130 male Sprague-Dawley rats were examined using a weight-drop model of TBI. The rats received the specific LRRK2 inhibitor PF-06447475 or LRRK2 pDNA alone or in combination with Drosha pDNA...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29521232/role-of-mir-193a-in-cancer-complexity-and-factors-control-the-pattern-of-its-expression
#13
Afraa Mamoori, Vinod Gopalan, Alfred K-Y Lam
BACKGROUND: There is emerging data suggest that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers. OBJECTIVE: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature. METHOD: All the literature concerning miR-193a in cancer in PubMed are analysed. RESULTS: Several studies proved the association of miR-193a expression patterns with cancer's stages, grades, response to the chemotherapy and even patient survival...
March 7, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29511594/imbalance-of-a-klf4-mir-7-auto-regulatory-feedback-loop-promotes-prostate-cancer-cell-growth-by-impairing-microrna-processing
#14
Lian-Zi Wei, Yan-Qing Wang, Yun-Li Chang, Na An, Xiao Wang, Pei-Jie Zhou, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
The microRNA-transcription factor auto-regulatory feedback loop is a pivotal mechanism for homeostatic regulation of gene expression, and dysregulation of the feedback loop is tightly associated with tumorigenesis and progression. However, the mechanism underlying such dysregulation is still not well-understood. Here we reported that Krüppel-like factor 4 (KLF4), a stemness-associated transcription factor, promotes the transcription of miR-7 to repress its own translation so that a KLF4-miR-7 auto-regulatory feedback loop is established for mutual regulation of their expression...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29509898/tsc2-regulates-microrna-biogenesis-via-mtorc1-and-gsk3%C3%AE
#15
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...
May 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29504892/comparing-mirna-structure-of-mirtrons-and-non-mirtrons
#16
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
https://www.readbyqxmd.com/read/29475968/mirna-processing-gene-methylation-and-cancer-risk
#17
Brian T Joyce, Yinan Zheng, Zhou Zhang, Lei Liu, Masha Kocherginsky, Robert Murphy, Chad J Achenbach, Jonah Musa, Firas Wehbe, Allan Just, Jincheng Shen, Pantel Vokonas, Joel Schwartz, Andrea A Baccarelli, Lifang Hou
Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection...
May 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29445371/effects-of-microrna-on-regulatory-t-cells-and-implications-for-adoptive-cellular-therapy-to-ameliorate-graft-versus-host-disease
#18
REVIEW
Keli L Hippen, Michael Loschi, Jemma Nicholls, Kelli P A MacDonald, Bruce R Blazar
Regulatory T cells (Tregs) are key mediators of the immune system. MicroRNAs (miRNAs) are a family of ~22 nucleotide non-coding RNAs that are processed from longer precursors by the RNases Drosha and Dicer. miRNA regulates protein expression posttranscriptionally through mRNA destabilization or translational silencing. A critical role for miRNA in Treg function was initially discovered when both Dicer and Drosha knockout (KO) mice were found to develop a fatal autoimmune disease phenotypically similar to Foxp3 KO mice...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29435107/discovery-and-functional-implications-of-a-mir-29b-1-mir-29a-cluster-polymorphism-in-acute-myeloid-leukemia
#19
Apollinaire Ngankeu, Parvathi Ranganathan, Violaine Havelange, Deedra Nicolet, Stefano Volinia, Bayard L Powell, Jonathan E Kolitz, Geoffrey L Uy, Richard M Stone, Steven M Kornblau, Michael Andreeff, Carlo M Croce, Clara D Bloomfield, Ramiro Garzon
We previously reported that microRNA (miR)-29b is down-regulated and has a tumor suppressor role in acute myeloid leukemia (AML). However, little is known about the mechanisms responsible for miR-29b expression downregulation in AML. In this work we screened for mutations that could affect miR-29b expression. Using Sanger sequencing, we identified a germline thymidine (T) base deletion within the miR-29b-1/miR-29a cluster precursor in 16% of AML patients. Remarkably we found a significant enrichment for the presence of the miR-29 polymorphism in core binding factor (CBF) newly diagnosed AML patients ( n = 61/303; 20%) with respect to age, sex and race matched controls ( n = 43/402:11%, P < 0...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29428937/high-throughput-data-of-circular-rna-profiles-in-human-temporal-cortex-tissue-reveals-novel-insights-into-temporal-lobe-epilepsy
#20
Jiaxin Li, Haijun Lin, Zhenrong Sun, Guanyi Kong, Xu Yan, Yujiao Wang, Xiaoxuan Wang, Yanhua Wen, Xiang Liu, Hongkun Zheng, Mei Jia, Zhongfang Shi, Rong Xu, Shaohua Yang, Fang Yuan
BACKGROUND/AIMS: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. METHODS: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients...
2018: Cellular Physiology and Biochemistry
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