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microRNA autoregulation

Avital Steiman-Shimony, Orr Shtrikman, Hanah Margalit
In human, nearly half of the known microRNAs (miRNAs) are encoded within the introns of protein-coding genes. The embedment of these miRNA genes within the sequences of protein-coding genes alludes to a possible functional relationship between intronic miRNAs and their hosting genes. Several studies, using predicted targets, suggested that intronic miRNAs influence their hosts' function either antagonistically or synergistically. New experimental data of miRNA expression patterns and targets enable exploring this putative association by relying on actual data rather than on predictions...
May 11, 2018: RNA
Johan Holmberg, Anirban Bhattachariya, Azra Alajbegovic, Catarina Rippe, Mari Ekman, Diana Dahan, Tran Thi Hien, Thomas Boettger, Thomas Braun, Karl Swärd, Per Hellstrand, Sebastian Albinsson
OBJECTIVE: Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood. APPROACH AND RESULTS: The importance of smooth muscle-enriched microRNAs, miR-143/145, for myogenic tone was evaluated in miR-143/145 knockout mice...
February 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Peisong Chen, Ting Shen, Huimin Wang, Zhiyong Ke, Yaru Liang, Juan Ouyang, Tang Jiang
Overexpression of microRNA-185-5p (miR-185-5p) in glucocorticoid (GC)-sensitive acute lymphoblastic leukemia (ALL) was identified using a microarray and reverse transcription polymerase chain reaction and was further confirmed in ALL cell lines. A reporter assay confirmed that the Rictor-one component of mammalian target of rapamycin complex 2 (mTORC2) is a target of miR-185-5p. Decreased mTORC activity was also confirmed in GC-sensitive patients. Overexpression of miR-185-5p significantly enhanced GC sensitivity in CEM-C1 cells (GC resistance) by increasing the rate of cell apoptosis and cycle arrest, and decreasing cell survival, accompanied by a decrease in mTORC activity and an increase in GC-induced glucocorticoid receptor (GR) expression...
February 28, 2017: Leukemia & Lymphoma
Jack Zhang, Andy Babic
The MET oncogene is a predictive biomarker and an attractive therapeutic target for various cancers. Its expression is regulated at multiple layers via various mechanisms. It is subject to epigenetic modifications, i.e. DNA methylation and histone acetylation. Hypomethylation and acetylation of the MET gene have been associated with its high expression in some cancers. Multiple transcription factors including Sp1 and Ets-1 govern its transcription. After its transcription, METmRNA is spliced into multiple species in the nucleus before being transported to the cytoplasm where its translation is modulated by at least 30 microRNAs and translation initiation factors, e...
April 2016: Carcinogenesis
Chun-Yu Cho, Jhy-Shrian Huang, Shine-Gwo Shiah, Shih-Ying Chung, Jong-Ding Lay, Ya-Yu Yang, Gi-Ming Lai, Ann-Lii Cheng, Li-Tzong Chen, Shuang-En Chuang
The AXL receptor tyrosine kinase is frequently overexpressed in cancers and is important in cancer invasion/metastasis and chemoresistance. Here, we demonstrate a regulatory feedback loop between AXL and microRNA (miRNA) at the post-transcriptional level. Both the GAS6-binding domain and the kinase domain of AXL, particularly the Y779 tyrosine phosphorylation site, are shown to be crucial for this autoregulation. To clarify the role of miRNAs in this regulation loop, approaches using bioinformatics and molecular techniques were applied, revealing that miR-34a may target the 3' UTR of AXL mRNA to inhibit AXL expression...
February 2016: RNA
Youning Wang, Lixiang Wang, Yanmin Zou, Liang Chen, Zhaoming Cai, Senlei Zhang, Fang Zhao, Yinping Tian, Qiong Jiang, Brett J Ferguson, Peter M Gresshoff, Xia Li
MicroRNAs are noncoding RNAs that act as master regulators to modulate various biological processes by posttranscriptionally repressing their target genes. Repression of their target mRNA(s) can modulate signaling cascades and subsequent cellular events. Recently, a role for miR172 in soybean (Glycine max) nodulation has been described; however, the molecular mechanism through which miR172 acts to regulate nodulation has yet to be explored. Here, we demonstrate that soybean miR172c modulates both rhizobium infection and nodule organogenesis...
December 2014: Plant Cell
Ya-Chung Tian, Yi-Jung Li, Hua-Chien Chen, Hsin-Hsu Wu, Cheng-Hao Weng, Yung-Chang Chen, Cheng-Chia Lee, Ming-Yang Chang, Hsiang-Hao Hsu, Tzung-Hai Yen, Cheng-Chieh Hung, Chih-Wei Yang
Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector...
May 9, 2014: Biochemical and Biophysical Research Communications
Mazhar Hussain, Sassan Asgari
MicroRNAs (miRNAs) are small regulatory RNAs that play significant roles in most cellular processes. In the seemingly endless arms race between hosts and pathogens, viruses also encode miRNAs that facilitate successful infection. In search of functional miRNAs or viral small RNAs (vsRNAs) encoded by Dengue virus (DENV), deep sequencing data of virus-infected Aedes aegypti mosquitoes were used. From six vsRNAs, with candidate stem-loop structures in the 5' and 3' untranslated regions of the viral genomic RNA, inhibition of DENV-vsRNA-5 led to significant increases in viral replication...
February 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
Aránzazu Chamorro-Jorganes, Elisa Araldi, Noemi Rotllan, Daniel Cirera-Salinas, Yajaira Suárez
MicroRNA-149 (miR-149) is located within the first intron of the glypican-1 (GPC1) gene. GPC1 is a low affinity receptor for fibroblast growth factor (FGF2) that enhances FGF2 binding to its receptor (FGFR1), subsequently promoting FGF2-FGFR1 activation and signaling. Using bioinformatic approaches, both GPC1 and FGFR1 were identified and subsequently validated as targets for miR-149 (both the mature strand, miR-149, and the passenger strand, miR-149*) in endothelial cells (ECs). As a consequence of their targeting activity towards GPC1 and FGFR1, both miR-149 and miR-149* regulated FGF2 signaling and FGF2-induced responses in ECs, namely proliferation, migration and cord formation...
March 15, 2014: Journal of Cell Science
Michael J Turner, Alan L Jiao, Frank J Slack
The conserved lin-4 microRNA (miRNA) regulates the proper timing of stem cell fate decisions in C. elegans by regulating stemness genes such as lin-14 and lin-28. (1)(-) (3) While lin-4 is upregulated toward the end of the first larval stage and functions as an essential developmental timing "switch", little is known about how lin-4 expression is regulated. (4) Here we show that in C. elegans hypodermal seam cells, transcription of lin-4 is positively regulated by lin-4 itself. In these cells, lin-4 activates its own transcription through a conserved lin-4-complementary element (LCE) in its promoter...
2014: Cell Cycle
Chun Jung Chen, Jennifer E Cox, Rodney P Kincaid, Angel Martinez, Christopher S Sullivan
Hundreds of virus-encoded microRNAs (miRNAs) have been uncovered, but an in-depth functional understanding is lacking for most. A major challenge for the field is separating those miRNA targets that are biologically relevant from those that are not advantageous to the virus. Here, we show that miRNAs from related variants of the polyomavirus simian vacuolating virus 40 (SV40) have differing host target repertoires (targetomes) while their direct autoregulatory activity on virus-encoded early gene products is completely preserved...
October 2013: Journal of Virology
Tina Toni, Bruce Tidor
Biological systems are inherently variable, with their dynamics influenced by intrinsic and extrinsic sources. These systems are often only partially characterized, with large uncertainties about specific sources of extrinsic variability and biochemical properties. Moreover, it is not yet well understood how different sources of variability combine and affect biological systems in concert. To successfully design biomedical therapies or synthetic circuits with robust performance, it is crucial to account for uncertainty and effects of variability...
2013: PLoS Computational Biology
Carla Bosia, Matteo Osella, Mariama El Baroudi, Davide Corà, Michele Caselle
BACKGROUND: MicroRNAs, post-transcriptional repressors of gene expression, play a pivotal role in gene regulatory networks. They are involved in core cellular processes and their dysregulation is associated to a broad range of human diseases. This paper focus on a minimal microRNA-mediated regulatory circuit, in which a protein-coding gene (host gene) is targeted by a microRNA located inside one of its introns. RESULTS: Autoregulation via intronic microRNAs is widespread in the human regulatory network, as confirmed by our bioinformatic analysis, and can perform several regulatory tasks despite its simple topology...
2012: BMC Systems Biology
Melissa L Wilbert, Stephanie C Huelga, Katannya Kapeli, Thomas J Stark, Tiffany Y Liang, Stella X Chen, Bernice Y Yan, Jason L Nathanson, Kasey R Hutt, Michael T Lovci, Hilal Kazan, Anthony Q Vu, Katlin B Massirer, Quaid Morris, Shawn Hoon, Gene W Yeo
LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28-binding sites in a quarter of human transcripts...
October 26, 2012: Molecular Cell
Dimitrios G Zisoulis, Zoya S Kai, Roger K Chang, Amy E Pasquinelli
MicroRNAs (miRNAs) comprise a large family of small RNA molecules that post-transcriptionally regulate gene expression in many biological pathways. Most miRNAs are derived from long primary transcripts that undergo processing by Drosha to produce ~65-nucleotide precursors that are then cleaved by Dicer, resulting in the mature 22-nucleotide forms. Serving as guides in Argonaute protein complexes, mature miRNAs use imperfect base pairing to recognize sequences in messenger RNA transcripts, leading to translational repression and destabilization of the target messenger RNAs...
June 28, 2012: Nature
Eva Matoulkova, Eva Michalova, Borivoj Vojtesek, Roman Hrstka
The untranslated regions (UTRs) at the 3'end of mRNA transcripts contain important sequences that influence the fate of mRNA and thus proteosynthesis. In this review, we summarize the information known to date about 3'end processing, sequence characteristics including related binding proteins and the role of 3'UTRs in several selected signaling pathways to delineate their importance in the regulatory processes in mammalian cells. In addition to reviewing recent advances in the more well known aspects, such as cleavage and polyadenylation processes that influence mRNA stability and location, we concentrate on some newly emerging concepts of the role of the 3'UTR, including alternative polyadenylation sites in relation to proliferation and differentiation and the recognition of the multi-functional properties of non-coding RNAs, including miRNAs that commonly target the 3'UTR...
May 2012: RNA Biology
Saikat Chakraborty, Shabana Mehtab, Anand Patwardhan, Yamuna Krishnan
MicroRNAs control gene expression either by RNA transcript degradation or translational repression. Expressions of miRNAs are highly regulated in tissues, disruption of which leads to disease. How this regulation is achieved and maintained is still largely unknown. MiRNAs that reside on clustered or polycistronic transcripts represent a more complex case where individual miRNAs from a cluster are processed with different efficiencies despite being cotranscribed. To shed light on the regulatory mechanisms that might be operating in these cases, we considered the long polycistronic primary miRNA transcript pri-miR-17-92a that contains six miRNAs with diverse functions...
May 2012: RNA
Mitsuo Kato, Laura Arce, Mei Wang, Sumanth Putta, Linda Lanting, Rama Natarajan
Enhanced transforming growth factor-β1 (TGF-β1) expression in renal cells promotes fibrosis and hypertrophy during the progression of diabetic nephropathy. The TGF-β1 promoter is positively controlled by the E-box regulators, upstream stimulatory factors (USFs), in response to diabetic (high glucose) conditions; however, it is not clear whether TGF-β1 is autoregulated by itself. As changes in microRNAs (miRNAs) have been implicated in kidney disease, we tested their involvement in this process. TGF-β1 levels were found to be upregulated by microRNA-192 (miR-192) or miR-200b/c in mouse mesangial cells...
August 2011: Kidney International
Chun Jung Chen, Rodney P Kincaid, Gil Ju Seo, Mark D Bennett, Christopher S Sullivan
Several different members of the Polyomaviridae, including some human pathogens, encode microRNAs (miRNAs) that lie antisense with respect to the early gene products, the tumor (T) antigens. These miRNAs negatively regulate T antigen expression by directing small interfering RNA (siRNA)-like cleavage of the early transcripts. miRNA mutant viruses of some members of the Polyomaviridae express increased levels of early proteins during lytic infection. However, the importance of miRNA-mediated negative regulation of the T antigens remains uncertain...
May 2011: Journal of Virology
Zhimin Ou, Taira Wada, Roberto Gramignoli, Song Li, Stephen C Strom, Min Huang, Wen Xie
The nuclear receptor liver X receptor (LXR) is a ligand-dependent transcription factor that plays an important role in the metabolism and homeostasis of cholesterol, lipids, bile acids, and steroid hormones. MicroRNAs (miRNAs) are recently recognized important negative regulators of gene expression. In this report, we showed that miRNA hsa-miR-613 played an important role in the autoregulation of the human LXRα gene. hsa-miR-613 targeted the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3'-untranslated region...
April 2011: Molecular Endocrinology
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