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Argonaute 4

Juan Liu, XueJiao Zhang, YueKun Yang, Ni Hong, GuoPing Wang, Aiming Wang, LiPing Wang
BACKGROUND: Heat treatment (known as thermotherapy) together with in vitro culture of shoot meristem tips is a commonly used technology to obtain virus-free germplasm for the effective control of virus diseases in fruit trees. RNA silencing as an antiviral defense mechanism has been implicated in this process. To understand if high temperature-mediated acceleration of the host antiviral gene silencing system in the meristem tip facilitates virus-derived small interfering RNAs (vsiRNA) accumulation to reduce the viral RNA titer in the fruit tree meristem tip cells, we used the Apple stem grooving virus (ASGV)-Pyrus pyrifolia pathosystem to explore the possible roles of vsiRNA in thermotherapy...
October 6, 2016: Virology Journal
Naoki Matsumoto, Hiroshi Nishimasu, Kazuhiro Sakakibara, Kazumichi M Nishida, Takamasa Hirano, Ryuichiro Ishitani, Haruhiko Siomi, Mikiko C Siomi, Osamu Nureki
PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 Å resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5' and 3' ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release...
October 6, 2016: Cell
Liduan Zheng, Wanju Jiao, Huajie Song, Hongxia Qu, Dan Li, Hong Mei, Yajun Chen, Feng Yang, Huanhuan Li, Kai Huang, Qiangsong Tong
Previous studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines...
2016: Cell Death & Disease
Laura Rivoli, A D Bastiaan Vliegenthart, Carmelita M J de Potter, Job J M H van Bragt, Nikolaos Tzoumas, Peter Gallacher, Tariq E Farrah, Neeraj Dhaun, James W Dear
AIM: microRNA-122 (miR-122) is a hepatotoxicity biomarker with utility in the management of paracetamol overdose and in drug development. Renal dysfunction and haemodialysis have been associated with a reduction in circulating microRNA. The objective of this study was to determine their effect on miR-122. METHODS: Blood samples were collected from 17 patients with end-stage renal disease (ESRD) on haemodialysis, 22 healthy controls, 30 patients with chronic kidney disease (CKD) and 15 patients post-kidney transplantation...
September 21, 2016: British Journal of Clinical Pharmacology
Catherine Schalk, Stephanie Drevensek, Amira Kramdi, Mohamed Kassam, Ikhlak Ahmed, Valerie Cognat, Stefanie Graindorge, Marc Bergdoll, Nicolas Baumberger, Dimitri Heintz, Chris Bowler, Pascal Genschik, Fredy Barneche, Vincent Colot, Jean Molinier
In eukaryotes, DNA repair pathways help to maintain genome integrity and epigenomic patterns. However, the factors at the nexus of DNA repair and chromatin modification/remodeling remain poorly characterized. Here, we uncover a previously unrecognized interplay between the DNA repair factor DNA DAMAGE-BINDING PROTEIN 2 (DDB2) and the DNA methylation machinery in Arabidopsis thaliana. Loss-of-function mutation in DDB2 leads to genome-wide DNA methylation alterations. Genetic and biochemical evidence indicate that at many repeat loci, DDB2 influences de novo DNA methylation by interacting with ARGONAUTE 4 (AGO4) and by controlling the local abundance of 24-nt short interfering RNAs (siRNAs)...
August 16, 2016: Plant Cell
Si Nian Char, Anjanasree K Neelakandan, Hartinio Nahampun, Bronwyn Frame, Marcy Main, Martin H Spalding, Philip W Becraft, Blake C Meyers, Virginia Walbot, Kan Wang, Bing Yang
CRISPR/Cas9 is a powerful genome editing tool in many organisms, including a number of monocots and dicots. Although the design and application of CRISPR/Cas9 is simpler compared to other nuclease-based genome editing tools, optimization requires consideration of the DNA delivery and tissue regeneration methods for a particular species to achieve accuracy and efficiency. Here, we describe a public sector system, ISU Maize CRISPR, utilizing Agrobacterium-delivered CRISPR/Cas9 for high-frequency targeted mutagenesis in maize...
August 11, 2016: Plant Biotechnology Journal
Yu Miyazaki, Xiaofei Du, Shin-Ichi Muramatsu, Christopher M Gomez
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by slowly progressive ataxia and Purkinje cell degeneration. SCA6 is caused by a polyglutamine repeat expansion within a second CACNA1A gene product, α1ACT. α1ACT expression is under the control of an internal ribosomal entry site (IRES) present within the CACNA1A coding region. Whereas SCA6 allele knock-in mice show indistinguishable phenotypes from wild-type littermates, expression of SCA6-associated α1ACT (α1ACTSCA6) driven by a Purkinje cell-specific promoter in mice produces slowly progressive ataxia and cerebellar atrophy...
July 13, 2016: Science Translational Medicine
Phillip A Angart, Rebecca J Carlson, Kwasi Adu-Berchie, S Patrick Walton
Efficient short interfering RNA (siRNA)-mediated gene silencing requires selection of a sequence that is complementary to the intended target and possesses sequence and structural features that encourage favorable functional interactions with the RNA interference (RNAi) pathway proteins. In this study, we investigated how terminal sequence and structural characteristics of siRNAs contribute to siRNA strand loading and silencing activity and how these characteristics ultimately result in a functionally asymmetric duplex in cultured HeLa cells...
July 11, 2016: Nucleic Acid Therapeutics
Scott R Suter, Jessica Sheu-Gruttadauria, Nicole T Schirle, Rachel Valenzuela, Alexi A Ball-Jones, Kazumitsu Onizuka, Ian J MacRae, Peter A Beal
Short interfering RNAs (siRNAs) are promising therapeutics that make use of the RNA interference (RNAi) pathway, but liabilities arising from the native RNA structure necessitate chemical modification for drug development. Advances in the structural characterization of components of the human RNAi pathway have enabled structure-guided optimization of siRNA properties. Here we report the 2.3 Å resolution crystal structure of human Argonaute 2 (hAgo2), a key nuclease in the RNAi pathway, bound to an siRNA guide strand bearing an unnatural triazolyl nucleotide at position 1 (g1)...
July 20, 2016: Journal of the American Chemical Society
Zhonghui Zhang, Xiuying Liu, Xinwei Guo, Xiu-Jie Wang, Xiuren Zhang
Argonaute (AGO) proteins recruit 21-24-nucleotide (nt) small RNAs (sRNAs) to constitute RNA-induced silencing complexes (RISCs) to regulate gene expression at transcriptional or posttranscriptional levels(1-3). Arabidopsis encodes nine functional AGO proteins. These proteins are classified into three clusters, AGO1/5/10, AGO2/3/7 and AGO4/6/9, based on their sequence similarity, functional redundancy, as well as species and features of AGO-bound sRNAs(4-7). Although most Arabidopsis AGO proteins have been studied well, AGO3-bound sRNAs and their basic function remain unknown...
2016: Nature Plants
Ming Yang, Yan Chen, Liangju Chen, Ke Wang, Tianying Pan, Xinghui Liu, Wenming Xu
INTRODUCTION: microRNAs (miRs) have been shown to play critical roles in the regulation of trophoblast and endothelial cell functions, and one significant finding concerning the miR-15/16 family is that most members of this family are highly expressed in endothelial cells and contribute to functions, such as tube formation. The interaction between trophoblast and endothelial cell play an important role in normal placentation process. Therefore, the aims of this study were to investigate the expression of miR-15b in human placenta and to uncover the potential role of miR-15b as well as its target functional loop in trophoblast and endothelial cells...
May 2016: Placenta
Nagendra Kumar Singh
microRNA (miRNA) is an endogenous and evolutionary conserved non-coding RNA, involved in post-transcriptional process as gene repressor and mRNA cleavage through RNA-induced silencing complex (RISC) formation. In RISC, miRNA binds in complementary base pair with targeted mRNA along with Argonaut proteins complex, causes gene repression or endonucleolytic cleavage of mRNAs and results in many diseases and syndromes. After the discovery of miRNA lin-4 and let-7, subsequently large numbers of miRNAs were discovered by low-throughput and high-throughput experimental techniques along with computational process in various biological and metabolic processes...
March 28, 2016: Interdisciplinary Sciences, Computational Life Sciences
Utpalendu Ghosh, Samit Adhya
Mammalian Argonaute proteins (AGO1-4), in combination with microRNAs (miRs), bind to target mRNAs to initiate degradation and/or translation repression, but the relationships between these two effects is unclear. Although the AGO isoforms ofDrosophilaand plants perform different functions, mammalian AGO isoforms are considered to be functionally degenerate in terms of miR loading and downstream silencing effects. However, we found that, in quiescent (G0) rat myoblasts transiting to the G1 phase, cyclin D1 (Ccnd1) mRNA was associated with two functionally distinct AGO-miR complexes...
March 25, 2016: Journal of Biological Chemistry
Shougang Sun, Jialiang Ma, Quan Zhang, Qiongying Wang, Lei Zhou, Feng Bai, Hao Hu, Peng Chang, Jing Yu, Bingren Gao
MicroRNAs (miRNAs) are a group of short, noncoding, regulatory RNA molecules the dysregulation of which contributes to the pathogenesis of myocarditis. Argonaute proteins are essential components of miRNA-induced silencing complex and play important roles during miRNA biogenesis and function. However, the expression pattern of four AGO family members has not yet been detected in the coxsackievirus B3 (CVB3)-induced myocarditis tissue samples. In this study, we detected the expression of four AGOs in the CVB3-infected mouse heart tissues and found that AGO1 and AGO3 up-regulated significantly at 4 and 8h after CVB3 infection...
March 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Ruiqiang Ye, Zulong Chen, Bi Lian, M Jordan Rowley, Ning Xia, Jijie Chai, Yan Li, Xin-Jian He, Andrzej T Wierzbicki, Yijun Qi
DNA methylation directed by 24-nucleotide (nt) small interfering RNAs (siRNAs) plays critical roles in gene regulation and transposon silencing in Arabidopsis. 24-nt siRNAs are known to be processed from double-stranded RNAs by Dicer-like 3 (DCL3) and loaded into the effector Argonaute 4 (AGO4). Here we report a distinct class of siRNAs independent of DCLs (sidRNAs). sidRNAs are present as ladders of ∼ 20-60 nt in length, often having the same 5' ends but differing in 3' ends by 1-nt steps. We further show that sidRNAs are associated with AGO4 and capable of directing DNA methylation...
January 21, 2016: Molecular Cell
Thomas C Roberts
MicroRNAs (miRNAs) are short (~22 nucleotides) single-stranded RNA molecules that primarily function to negatively regulate gene expression at the post-transcriptional level. miRNAs have thus been implicated in the regulation of a wide variety of normal cell functions and pathophysiological conditions. The miRNA machinery consists of a series of protein complexes which act to: (1) cleave the precursor-miRNA hairpin from its primary transcript (i.e. DROSHA and DGCR8); (2) traffic the miRNA hairpin between nucleus and cytoplasm (i...
2015: Advances in Experimental Medicine and Biology
Jing Zhao, Rong Luo, Xindong Xu, Ying Zou, Qingfeng Zhang, Weiqing Pan
BACKGROUND: Schistosomiasis, caused by schistosomes, is one of the most prevalent and serious parasitic diseases in tropical and subtropical countries. This pathogen has a complex life cycle and harbors a unique repertoire of genes expressed at different life-stages. Understanding the gene regulation of schistosomes will contribute to identification of novel drug targets and vaccine candidates. Some conserved and novel microRNAs (miRNAs) have been identified in schistosomes as key transcriptional and post-transcriptional regulators in the past few years; however, little is known about their specific targets...
2015: Parasites & Vectors
Rebecca De Santis, Anke Liepelt, Jana C Mossanen, Anne Dueck, Nadine Simons, Antje Mohs, Christian Trautwein, Gunter Meister, Gernot Marx, Antje Ostareck-Lederer, Dirk H Ostareck
To secure the functionality of activated macrophages in the innate immune response, efficient life span control is required. Recognition of bacterial lipopolysaccharides (LPS) by toll-like receptor 4 (TLR4) induces downstream signaling pathways, which merge to induce the expression of cytokine genes and anti-apoptotic genes. MicroRNAs (miRNAs) have emerged as important inflammatory response modulators, but information about their functional impact on apoptosis is scarce. To identify miRNAs differentially expressed in response to LPS, cDNA libraries from untreated and LPS-activated murine macrophages were analyzed by deep sequencing and regulated miRNA expression was verified by Northern blotting and qPCR...
January 2, 2016: RNA Biology
Zhi-Wei Guo, Chen Xie, Jian-Rong Yang, Jun-Hao Li, Jian-Hua Yang, Limin Zheng
MicroRNAs (miRNAs) play an important role in the regulation of gene expression. Previous studies on miRNA functions mainly focused on their target sites in the 3' untranslated regions (UTRs) of mRNAs. However, increasing evidence has revealed that miRNAs can also induce mRNA degradation and mediate translational repression via complementary interactions with the coding sequence (CDS) and 5'UTR of mRNAs. In this study, we developed a novel database, MtiBase, to facilitate the comprehensive exploration of CDS- and 5'UTR-located miRNA target sites identified from cross-linking immunoprecipitation sequencing (CLIP-Seq) datasets and to uncover their regulatory effects on mRNA stability and translation from expression profile datasets...
2015: Database: the Journal of Biological Databases and Curation
June Hyun Park, Chanseok Shin
Small RNA silencing is mediated by the effector RNA-induced silencing complex (RISC) that consists of an Argonaute protein (AGOs 1-4 in humans). A fundamental step during RISC assembly involves the separation of two strands of a small RNA duplex, whereby only the guide strand is retained to form the mature RISC, a process not well understood. Despite the widely accepted view that 'slicer-dependent unwinding' via passenger-strand cleavage is a prerequisite for the assembly of a highly complementary siRNA into the AGO2-RISC, here we show by careful re-examination that 'slicer-independent unwinding' plays a more significant role in human RISC maturation than previously appreciated, not only for a miRNA duplex, but, unexpectedly, for a highly complementary siRNA as well...
October 30, 2015: Nucleic Acids Research
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