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https://www.readbyqxmd.com/read/28283057/super-enhancer-mediated-rna-processing-revealed-by-integrative-microrna-network-analysis
#1
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/28266707/the-agotrons-gene-regulators-or-argonaute-protectors
#2
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/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
#3
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/28214904/rs10719-polymorphism-located-within-drosha-3-untranslated-region-is-responsible-for-development-of-primary-hypertension-by-disrupting-binding-with-microrna-27b
#4
Yabing Zhang, Ai-Lin Cao, Chun Dong
BACKGROUND MiR-27b is reportedly involved with many diseases (e.g., gastric cancer) by acting on different signaling pathways. In this study, we aimed at understanding the relationship between miR-27b and hypertension and its underlying molecular mechanism. MATERIAL AND METHODS Peripheral blood was collected from patients with hypertension, and statistical analysis was performed to study the association between rs10719 and risk of hypertension. Tissue samples were collected from patients with lung cancer, and the expression of miR-27b and DROSHA was determined using Western blot analysis and real-time PCR...
February 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28174021/biogenesis-and-function-of-ago-associated-rnas
#5
REVIEW
Iben Daugaard, Thomas Birkballe Hansen
Numerous sophisticated high-throughput sequencing technologies have been developed over the past decade, and these have enabled the discovery of a diverse catalog of small non-coding (nc)RNA molecules that function as regulatory entities by associating with Argonaute (Ago) proteins. MicroRNAs (miRNAs) are currently the best-described class of post-transcriptional regulators that follow a specific biogenesis pathway characterized by Drosha/DGCR8 and Dicer processing. However, more exotic miRNA-like species that bypass particular steps of the canonical miRNA biogenesis pathway continue to emerge, with one of the most recent additions being the agotrons, which escape both Drosha/DGCR8- and Dicer-processing...
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28158788/a-novel-role-for-gsk3%C3%AE-as-a-modulator-of-drosha-microprocessor-activity-and-microrna-biogenesis
#6
Claire E Fletcher, Jack D Godfrey, Akifumi Shibakawa, Martin Bushell, Charlotte L Bevan
No abstract text is available yet for this article.
October 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/28148795/hepatitis-b-virus-encoded-mirna-controls-viral-replication
#7
Xi Yang, Hongfeng Li, Huahui Sun, Hongxia Fan, Yaqi Hu, Min Liu, Xin Li, Hua Tang
microRNAs (miRNAs) are a class of small single-stranded non-coding functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA virus with virions and subviral forms of particles that lack a core. It was not known whether HBV encodes miRNAs. Here, we identified an HBV-encoded miRNA (called HBV-miR-3) by deep sequencing and northern blot. HBV-miR-3 is located at nts 373-393 of the HBV genome and was generated from 3.5Kb, 2,4Kb and 2.1Kb HBV in classic miRNA biogenesis (Drosha-Dicer dependent) manner. HBV-miR-3 was highly expressed in hepatoma cell lines with an integrated HBV genome and HBV (+) hepatoma tumors...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28111020/the-functional-cycle-of-rnt1p-five-consecutive-steps-of-double-stranded-rna-processing-by-a-eukaryotic-rnase-iii
#8
He Song, Xianyang Fang, Lan Jin, Gary X Shaw, Yun-Xing Wang, Xinhua Ji
Double-stranded RNA (dsRNA)-specific RNase III proteins are required for RNA maturation and gene regulation. The mechanism of prokaryotic RNase IIIs has been well characterized, but how eukaryotic RNase IIIs (exemplified by Rnt1p, Drosha, and Dicer) work is less clear. Recently, we reported the crystal structure of Rnt1p in complex with RNA, revealing a double-ruler mechanism for substrate selection. Here, we present more structures of Rnt1p, either RNA free or RNA bound, featuring two major conformations of the enzyme...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28098889/isomir-expression-patterns-in-canonical-and-dicer%C3%A2-independent-micrornas
#9
Tingming Liang, Jiafeng Yu, Chang Liu, Li Guo
Multiple microRNA (miRNA) variants, known as isomiRs, are extensively distributed in miRNA loci and predominantly derive from the alternative cleavage of Drosha/Dicer and 3'addition events. The present study aimed to investigate the expression patterns of multiple isomiRs in typical miRNA and Dicer‑independent miRNA loci by conducting evolutionary and expression analysis using public datasets. Although different miRNA maturation processes exist, multiple isomiRs can be detected by similar expression distributions...
January 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28053119/short-intron-derived-ncrnas
#10
Florent Hubé, Damien Ulveling, Alain Sureau, Sabrina Forveille, Claire Francastel
Introns represent almost half of the human genome, although they are eliminated from transcripts through RNA splicing. Yet, different classes of non-canonical miRNAs have been proposed to originate directly from intron splicing. Here, we considered the alternative splicing of introns as an interesting source of miRNAs, compatible with a developmental switch. We report computational prediction of new Short Intron-Derived ncRNAs (SID), defined as precursors of smaller ncRNAs like miRNAs and snoRNAs produced directly by splicing, and tested their dependence on each key factor in canonical or alternative miRNAs biogenesis (Drosha, DGCR8, DBR1, snRNP70, U2AF65, PRP8, Dicer, Ago2)...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27941919/multiplex-crispr-cas9-based-genome-engineering-enhanced-by-drosha-mediated-sgrna-shrna-structure
#11
Qiang Yan, Kun Xu, Jiani Xing, Tingting Zhang, Xin Wang, Zehui Wei, Chonghua Ren, Zhongtian Liu, Simin Shao, Zhiying Zhang
The clustered regularly interspaced short palindromic repeats (CRISPR) system has recently been developed into a powerful genome-editing technology, as it requires only two key components (Cas9 protein and sgRNA) to function and further enables multiplex genome targeting and homology-directed repair (HDR) based precise genome editing in a wide variety of organisms. Here, we report a novel and interesting strategy by using the Drosha-mediated sgRNA-shRNA structure to direct Cas9 for multiplex genome targeting and precise genome editing...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928938/sequence-and-structure-based-analysis-of-proteins-involved-in-mirna-biogenesis
#12
Chhaya Sharma, Debasisa Mohanty
miRNA biogenesis is a multistage process for the generation of a mature miRNA and involves several different proteins. In this work, we have carried out both sequence- and structure-based analysis for crucial proteins involved in miRNA biogenesis, namely Dicer, Drosha, Argonaute (Ago), and Exportin-5 to understand evolution of these proteins in animal kingdom and also to identify key sequence and structural features that are determinants of their function. Our analysis reveals that in animals the miRNA biogenesis pathway first originated in molluscs...
January 4, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27907888/a-novel-role-for-gsk3%C3%AE-as-a-modulator-of-drosha-microprocessor-activity-and-microrna-biogenesis
#13
Claire E Fletcher, Jack D Godfrey, Akifumi Shibakawa, Martin Bushell, Charlotte L Bevan
Regulation of microRNA (miR) biogenesis is complex and stringently controlled. Here, we identify the kinase GSK3β as an important modulator of miR biogenesis at Microprocessor level. Repression of GSK3β activity reduces Drosha activity toward pri-miRs, leading to accumulation of unprocessed pri-miRs and reduction of pre-miRs and mature miRs without altering levels or cellular localisation of miR biogenesis proteins. Conversely, GSK3β activation increases Drosha activity and mature miR accumulation. GSK3β achieves this through promoting Drosha:cofactor and Drosha:pri-miR interactions: it binds to DGCR8 and p72 in the Microprocessor, an effect dependent upon presence of RNA...
October 23, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#14
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27835943/precise-mapping-of-the-transcription-start-sites-of-human-micrornas-using-drosha-knockout-cells
#15
Geon Jeong, Yeong-Hwan Lim, Young-Kook Kim
BACKGROUND: The expression of microRNAs (miRNAs) is primarily regulated during their transcription. However, the transcriptional regulation of miRNA genes has not been studied extensively owing to the lack of sufficient information about the promoters and transcription start sites of most miRNAs. RESULTS: In this study, we identified the transcription start sites of human primary miRNAs (pri-miRNAs) using DROSHA knockout cells. DROSHA knockout resulted in increased accumulation of pri-miRNAs and facilitated the precise mapping of their 5' end nucleotides using the rapid amplification of cDNA ends (RACE) technique...
November 11, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27808570/dicer-and-drosha-gene-expression-and-polymorphisms-in-autoimmune-thyroid-diseases
#16
Minori Saeki, Mikio Watanabe, Naoya Inoue, Ena Tokiyoshi, Yukina Takuse, Yuya Arakawa, Yoh Hidaka, Yoshinori Iwatani
Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method...
November 3, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27796942/comparison-of-mirna-profiling-during-airway-epithelial-repair-in-undifferentiated-and-differentiated-cells-in-vitro
#17
Wojciech Langwinski, Beata Narozna, Peter M Lackie, John W Holloway, Aleksandra Szczepankiewicz
Respiratory epithelium is a highly integrated structure that efficiently protects lungs from extrinsic irritants thanks to rapid repair of the wound. The repair is a complex process that requires coordinated expression of networks of genes. Plausible regulators of this process are microRNAs. We investigated whether global miRNA silencing influences the epithelial repair, and whether changes in miRNA expression profile during repair are similar between two bronchial epithelial cell cultures: differentiated and undifferentiated cells...
October 28, 2016: Journal of Applied Genetics
https://www.readbyqxmd.com/read/27769040/microrna-like-viral-small-rna-from-porcine-reproductive-and-respiratory-syndrome-virus-negatively-regulates-viral-replication-by-targeting-the-viral-nonstructural-protein-2
#18
Na Li, Yunhuan Yan, Angke Zhang, Jiming Gao, Chong Zhang, Xue Wang, Gaopeng Hou, Gaiping Zhang, Jinbu Jia, En-Min Zhou, Shuqi Xiao
Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification...
October 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27766492/co-and-no-bind-to-fe-ii-digeorge-critical-region-8-heme-but-do-not-restore-primary-microrna-processing-activity
#19
Judy P Hines, Aaron T Smith, Jose P Jacob, Gudrun S Lukat-Rodgers, Ian Barr, Kenton R Rodgers, Feng Guo, Judith N Burstyn
The RNA-binding heme protein DiGeorge critical region 8 (DGCR8) and its ribonuclease partner Drosha cleave primary transcripts of microRNA (pri-miRNA) as part of the canonical microRNA (miRNA) processing pathway. Previous studies show that bis-cysteine thiolate-coordinated Fe(III) DGCR8 supports pri-miRNA processing activity, while Fe(II) DGCR8 does not. In this study, we further characterized Fe(II) DGCR8 and tested whether CO or NO might bind and restore pri-miRNA processing activity to the reduced protein...
October 20, 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27762676/canonical-micrornas-enable-differentiation-protect-against-dna-damage-and-promote-cholesterol-biosynthesis-in-neural-stem-cells
#20
Zhong Liu, Cheng Zhang, Alireza Khodadadi-Jamayran, Lam Dang, Xiaosi Han, Kitai Kim, Hu Li, Rui Zhao
Neural stem cells (NSCs) have the capacity to differentiate into neurons, astrocytes, and oligodendrocytes, and therefore represent a promising donor tissue source for treating neurodegenerative diseases and repairing injuries of the nervous system. However, it remains unclear how canonical microRNAs (miRNAs), the subset of miRNAs requiring the Drosha-Dgcr8 microprocessor and the type III RNase Dicer for biogenesis, regulate NSCs. In this study, we established and characterized Dgcr8(-/-) NSCs from conditionally Dgcr8-disrupted mouse embryonic brain...
February 1, 2017: Stem Cells and Development
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