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https://www.readbyqxmd.com/read/28431232/genome-wide-mapping-of-drosha-cleavage-sites-on-primary-micrornas-and-noncanonical-substrates
#1
Baekgyu Kim, Kyowon Jeong, V Narry Kim
MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gatekeeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here, we establish a protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single-nucleotide resolution...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28404517/dysregulation-of-microrna-biogenesis-in-the-small-intestine-after-ethanol-and-burn-injury
#2
Niya L Morris, Adam M Hammer, Abigail R Cannon, Robin C Gagnon, Xiaoling Li, Mashkoor A Choudhry
Ethanol exposure at the time of burn injury is a major contributor to post-burn pathogenesis. Many of the adverse effects associated with ethanol and burn injury are linked to an impaired intestinal barrier. The combined insult causes intestinal inflammation, resulting in tissue damage, altered tight junction expression, and increased intestinal permeability. MicroRNAs play a critical role in maintaining intestinal homeostasis including intestinal inflammation and barrier function. Specifically, miR-150 regulates inflammatory mediators which can contribute to gut barrier disruption...
April 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28400409/drosha-targets-its-own-transcript-to-modulate-alternative-splicing
#3
Dooyoung Lee, Jin-Wu Nam, Chanseok Shin
The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts. Apart from its central role in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA-like hairpins in a subset of transcripts without apparent small RNA production. Here, we report that the human DROSHA transcript is one such non-canonical target of DROSHA. Mammalian DROSHA genes have evolved a conserved hairpin structure spanning a specific exon-intron junction, which serves as a substrate for the Microprocessor in human cells but not in murine cells...
April 11, 2017: RNA
https://www.readbyqxmd.com/read/28399989/endo-sirna-deficiency-results-in-oocyte-maturation-failure-and-apoptosis-in-porcine-oocytes
#4
Wanxin Liu, Qi Zhao, Shanhua Piao, Chunsheng Wang, Qingran Kong, Tiezhu An
Both microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs) play key regulatory roles in gene expression. Some studies have demonstrated that the function of miRNA is suppressed in mouse oocytes, suggesting that endo-siRNA, not miRNA, is essential for female meiosis. This finding has yet to be confirmed in other species. In this study, by knockdown of DICER1, DROSHA and its cofactor DiGeorge syndrome critical region 8 (DGCR8) in porcine oocytes, we found that the proportion of oocytes with DICER1 deficiency that developed to meiosis II (MII) stage was significantly lower than oocytes with DROSHA and DGCR8 deficiency (39...
April 12, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28388330/yellow-fever-virus-modulates-the-expression-of-key-proteins-related-to-the-microrna-pathway-in-the-human-hepatocarcinoma-cell-line-hepg2
#5
Gustavo Moraes Holanda, Samir Mansour Moraes Casseb, Karla Fabiane Lopes Mello, Pedro Fernando Costa Vasconcelos, Ana Cecília Ribeiro Cruz
Yellow fever is a zoonotic disease caused by the yellow fever virus (YFV) and transmitted by mosquitoes of the family Culicidae. It is well known that cellular and viral microRNAs (miRNAs) are involved in modulation of viral and cellular gene expression, as well as immune response, and are considered by the scientific community as possible targets for an effective therapy against viral infections. This regulation may be involved in different levels of infection and clinical symptomatology. We used viral titration techniques, viral kinetics from 24 to 96 hours postinfection (hpi), and analyzed the expression of key proteins related to the miRNA pathway by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)...
April 7, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28388279/investigation-of-aid-dicer-and-drosha-expressions-in-patients-with-chronic-lymphocytic-leukemia
#6
Metin Yusuf Gelmez, Ender Coskunpinar, Basak Saracoglu, Gunnur Deniz, Melih Aktan
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. Cytogenetic lesions such as del13q14, del11q22.3, and del17p13 are identified in 50-60% of patients. Activation-induced cytidine deaminase (AID) plays a central role in somatic hyper mutation (SHM) and class switch recombination (CSR) and functions on Ig genes, but also target non-Ig genes, and over-expression of AID can lead to point mutations or translocations in non-Ig genes such as IgH/Myc translocation. Dicer and Drosha, which have a role in activation process of miRNA, also act in a double-strand DNA break (DSB) repair mechanism...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28380355/dgcr8-mediates-repair-of-uv-induced-dna-damage-independently-of-rna-processing
#7
Philamer C Calses, Kiranjit K Dhillon, Nyka Tucker, Yong Chi, Jen-Wei Huang, Masaoki Kawasumi, Paul Nghiem, Yemin Wang, Bruce E Clurman, Celine Jacquemont, Philip R Gafken, Kaoru Sugasawa, Masafumi Saijo, Toshiyasu Taniguchi
Ultraviolet (UV) radiation is a carcinogen that generates DNA lesions. Here, we demonstrate an unexpected role for DGCR8, an RNA binding protein that canonically functions with Drosha to mediate microRNA processing, in the repair of UV-induced DNA lesions. Treatment with UV induced phosphorylation on serine 153 (S153) of DGCR8 in both human and murine cells. S153 phosphorylation was critical for cellular resistance to UV, the removal of UV-induced DNA lesions, and the recovery of RNA synthesis after UV exposure but not for microRNA expression...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28358001/sgk1-affects-ran-ranbp1-rangap1-via-sp1-to-play-a-critical-role-in-pre-mirna-nuclear-export-a-new-route-of-epigenomic-regulation
#8
Vincenzo Dattilo, Lucia D'Antona, Cristina Talarico, Mjriam Capula, Giada Catalogna, Rodolfo Iuliano, Silvia Schenone, Sante Roperto, Cataldo Bianco, Nicola Perrotti, Rosario Amato
The serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28352639/racial-differences-in-expression-levels-of-mirna-machinery-related-genes-dicer-drosha-dgcr8-and-ago2-in-asian-korean-papillary-thyroid-carcinoma-and-comparative-validation-using-the-cancer-genome-atlas
#9
Jaegil Kim, Woo-Jae Park, Kwang-Joon Jeong, Sun Hee Kang, Sun Young Kwon, Shin Kim, Jong-Wook Park
Aberrant regulation of microRNA (miRNA) machinery components is associated with various human cancers, including papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer, and a higher prevalent female malignancy. The purpose of this study is to investigate racial differences in mRNA expression levels of four miRNA machinery components, Dicer, Drosha, DGCR8, and AGO2, and their correlations with clinicopathological characteristics. Forty PTC samples from female Asian Korean PTC patients were enrolled...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28347890/microrna-328-is-involved-in-wound-repair-process-in-human-bronchial-epithelial-cells
#10
Beata Narożna, Wojciech Langwinski, Claire Jackson, Peter Lackie, John W Holloway, Aleksandra Szczepankiewicz
Our aim was to investigate the role of microRNA on epithelial wound repair by global microRNA silencing. We have also analysed the influence of five miRNAs (miR-328, miR-342, miR-411, miR-609, miR-888, previously identified) on wound repair in 16HBE14o-bronchial epithelial cell line. Cells were transfected with siRNAs against human DROSHA and DICER1 or miRNA mimics or inhibitors. Wounding assays were performed and the cells were observed using time-lapse microscopy. The area of damage was calculated at chosen time points, followed by data analysis...
March 25, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28342199/overexpression-of-drosha-digeorge-syndrome-critical-region-gene-8-dgcr8-and-dicer-mrnas-in-the-pathogenesis-of-psoriasis
#11
Majid Rostami Mogaddam, Nastaran Safavi Ardabili, Yousef Shafaeei, Nasrollah Maleki, Naser Jafari, Alireza Jafari
INTRODUCTION: Psoriasis is a complex autoimmune inflammatory disease that occurs in genetically susceptible individuals and presents with the development of inflammatory plaques on the skin. Recent studies have indicated that microRNAs (miRNAs) play important roles in psoriasis. OBJECTIVE: To investigate whether expression of Drosha, DGCR8, and Dicer mRNAs is involved in the pathogenesis of psoriasis. METHODS: Biopsies were obtained from involved psoriatic skin (PP), noninvolved psoriatic skin (PN), and healthy skin (NN)...
March 25, 2017: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/28340815/expression-profile-of-microrna-biogenesis-components-in-renal-transplant-patients
#12
E Celen, M G Ertosun, H Kocak, A Dinckan, B Yoldas
BACKGROUND: MicroRNAs (miRNAs) and the miRNA biogenesis components are potential biomarkers of some prevalent diseases, such as cancer and diabetes. In light of this information, we aimed to investigate the expression profiles of miRNA biogenesis components in renal transplant patients before and after transplantation and how these profiles are related to immunosuppressive treatment and clinical outcomes of these patients. METHODS: In this study, gene and protein expression profiles of Dicer, Drosha, Pasha (DGCR8), Exportin5 (XPO5), and Argonaute2 (AGO2) in peripheral blood mononuclear cells (PBMCs) of renal transplant patients were evaluated by means of real-time quantitative polymerase chain reaction and Western blot methods before and 3 months after transplantation...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28283057/super-enhancer-mediated-rna-processing-revealed-by-integrative-microrna-network-analysis
#13
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
#14
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
#15
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
#16
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
#17
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...
March 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
#18
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
#19
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
#20
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
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