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https://www.readbyqxmd.com/read/28540674/microrna-expression-protein-participants-in-microrna-regulation
#1
Valeria M King, Glen M Borchert
MiRNAs are ~20 nt small RNAs that regulate networks of proteins using a seed region of nucleotides 2-8 to complement the 3' UTR of target mRNAs. The biogenesis and function of miRNAs as translational repressors is facilitated by protein counterparts that process primary and precursor miRNAs to maturity (Drosha/DCGR8 and Dicer/TRBP respectively) and incorporate miRNAs into the protein complex RISC to recognize and repress target mRNAs (RISC proteins: Ago/TRBP1/TRBP2/DICER). Similarly, siRNAs through comparable mechanisms are loaded into the protein complex RITS to heterochromatin formation of DNA and suppress transcription of particular genes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28522832/the-fragment-hmga2-sh-3p20-from-hmga2-mrna-3-utr-promotes-the-growth-of-hepatoma-cells-by-upregulating-hmga2
#2
Yuan Wang, Fuquan Chen, Zhe Yang, Man Zhao, Shuqin Zhang, Yuen Gao, Jinyan Feng, Guang Yang, Weiying Zhang, Lihong Ye, Xiaodong Zhang
High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507100/the-microrna-machinery-regulates-fasting-induced-changes-in-gene-expression-and-longevity-in-caenorhabditis-elegans
#3
Akiko Kogure, Masaharu Uno, Takako Ikeda, Eisuke Nishida
Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (approximately 22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28499456/role-of-micrornas-in-premature-ovarian-insufficiency
#4
REVIEW
Ying Guo, Junyan Sun, Dongmei Lai
Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting for a minimum of 4 months. The typical characteristics comprised of declined estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in women <40-year-old, primarily originating from iatrogenic factors, karyotypic abnormalities, and genetic factors. However, the etiology of POI remains unknown in approximately 90% of cases. POI could lead to infertility, osteoporosis, cardiovascular disorder, and cognitive dysfunction...
May 12, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28486664/microrna-21-plays-a-pivotal-role-in-the-oocyte-secreted-factor-induced-suppression-of-cumulus-cell-apoptosis%C3%A2
#5
Xiao Han, Rui Xue, Hong-Jie Yuan, Tian-Yang Wang, Juan Lin, Jie Zhang, Bo Liang, Jing-He Tan
It is known that oocytes and cumulus cells (CCs) are more resistant to apoptosis than other compartments of the antral follicle. However, although oocyte-secreted factors (OSFs) have been found to be involved in suppressing bovine CC apoptosis, little is known about the intra-cellular mechanisms by which OSFs render CCs resistant to apoptosis. Here we show that coculture with mouse or pig cumulus-denuded oocytes, culture with recombinant mouse growth differentiation factor-9 (GDF-9) or culture in pig oocyte-conditioned medium (POCM) significantly inhibited CC apoptosis of mouse oocytectomized cumulus oophorus complexes (OOXs)...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28483554/downregulation-of-mir-192-causes-hepatic-steatosis-and-lipid-accumulation-by-inducing-srebf1-novel-mechanism-for-bisphenol-a-triggered-non-alcoholic-fatty-liver-disease
#6
Yi Lin, Dongxiao Ding, Qiansheng Huang, Qiong Liu, Haoyang Lu, Yanyang Lu, Yulang Chi, Xia Sun, Guozhu Ye, Huimin Zhu, Jie Wei, Sijun Dong
Exposure to Bisphenol A (BPA) has been associated with the development of non-alcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and whether lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50μg/kg/day of BPA by oral gavage for 90days displayed a NAFLD-like phenotype...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28466845/genetic-variation-and-rna-structure-regulate-microrna-biogenesis
#7
Noemi Fernandez, Ross A Cordiner, Robert S Young, Nele Hug, Sara Macias, Javier F Cáceres
MiRNA biogenesis is highly regulated at the post-transcriptional level; however, the role of sequence and secondary RNA structure in this process has not been extensively studied. A single G to A substitution present in the terminal loop of pri-mir-30c-1 in breast and gastric cancer patients had been previously described to result in increased levels of mature miRNA. Here, we report that this genetic variant directly affects Drosha-mediated processing of pri-mir-30c-1 in vitro and in cultured cells. Structural analysis of this variant revealed an altered RNA structure that facilitates the interaction with SRSF3, an SR protein family member that promotes pri-miRNA processing...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461238/functional-analysis-of-microrna-pathway-genes-in-the-somatic-gonad-and-germ-cells-during-ovulation-in-c-elegans
#8
Carmela Rios, David Warren, Benjamin Olson, Allison L Abbott
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play critical roles in animal development and physiology, though functions for most miRNAs remain unknown. Worms with reduced miRNA biogenesis due to loss of Drosha or Pasha/DGCR8 activity are sterile and fail to ovulate, indicating that miRNAs are required for the process of oocyte maturation and ovulation. Starting with this penetrant sterile phenotype and using new strains created to perform tissue specific RNAi, we characterized the roles of the C...
June 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28448850/perturbation-of-drosha-and-dicer-expression-by-human-papillomavirus-16-oncoproteins
#9
Mallory E Harden, Karl Munger
Many tumors, including cervical carcinoma, show dysregulated expression of the microRNA processing machinery, specifically DROSHA and DICER. Some cervical cancers exhibit chromosome 5p amplifications and DROSHA is the most significantly upregulated transcript and is observed in all tumors with 5p gain. DROSHA and DICER mRNA levels, however, are higher in HPV positive cancer lines than in an HPV negative cervical carcinoma line. We show that high-risk HPV E6/E7 expression in HPV negative C33A cervical carcinoma cells and primary human epithelial cell causes increased expression of DROSHA and DICER mRNA and protein...
July 2017: Virology
https://www.readbyqxmd.com/read/28431232/genome-wide-mapping-of-drosha-cleavage-sites-on-primary-micrornas-and-noncanonical-substrates
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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