共查询到20条相似文献,搜索用时 31 毫秒
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RNA-mediated gene silencing 总被引:21,自引:0,他引:21
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Assel Mussabekova Laurent Daeffler Jean-Luc Imler 《Cellular and molecular life sciences : CMLS》2017,74(11):2039-2054
The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations. 相似文献
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Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result
in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures
the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints.
When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient
time for DNA repair. Since the term “checkpoint” was coined over 20 years ago, our understanding of the molecular mechanisms
governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans.
Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these
complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA
damage and preserve genome stability in eukaryotic cells. 相似文献
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Emerging connections between DNA methylation and histone acetylation 总被引:18,自引:0,他引:18
Modifications of both DNA and chromatin can affect gene expression and lead to gene silencing. Evidence of links between DNA methylation and histone hypoacetylation is accumulating. Several proteins that specifically bind to methylated DNA are associated with complexes that include histone deacetylases (HDACs). In addition, DNA methyltransferases of mammals appear to interact with HDACs. Experiments with animal cells have shown that HDACs are responsible for part of the repressive effect of DNA methylation. Evidence was found in Neurospora that protein acetylation can in some cases affect DNA methylation. The available data suggest that the roles of DNA methylation and histone hypoacetylation, and their relationship with each other, can vary, even within an organism. Some open questions in this emerging field that should be answered in the near future are discussed. 相似文献
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Aphasizhev R 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2194-2203
The terminal RNA uridylyltransferases (TUTases) catalyze transfer of UMP residues to the 3' hydroxyl group of RNA. These activities are widespread among eukaryotes and appear to be involved in a variety of RNA-processing pathways. Recent studies of RNA editing in trypanosomatids have provided the first insights into the biological functions of RNA uridylyltransferases, which had eluded biochemical identification despite 30-year-old evidence of such activities in mammals and plants. Comparative sequence analysis of trypanosomal TUTases and their homologs revealed by large-scale genomic projects demonstrates a significant level of biochemical and structural diversity between putative uridylyltransferases. The conserved catalytic domain has acquired additional protein modules and appears to have adapted to perform functionally distinct tasks of guided U-insertion into mRNA and constrained addition of an oligo[U] tail to guide RNAs. Here I discuss the current knowledge of this novel enzyme family and possible roles of RNA uridylylation in the regulation of gene expression. 相似文献
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Norma P. Williams D. Mukhopadhyay S. K. Dutta 《Cellular and molecular life sciences : CMLS》1981,37(11):1157-1158
Summary DNA:DNA hybridization studies of the homothallic species ofNeurospora showed that the repeated DNA sequences provided no means of distinction among them. Hybridization with nonrepeated DNA sequences, however, showed that theN. terricola species was quite unlike the others. These studies suggest that heterothallism might have evolved from homothallism inNeurospora.Supported in part by a contract with the US Department of Energy. We are grateful to Dr Lafayette Frederick of this Department for helping us with the cultures ofN. terricola andN. galapagosensis. 相似文献
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Valentina Libri Pascal Miesen Ronald P. van Rij Amy H. Buck 《Cellular and molecular life sciences : CMLS》2013,70(19):3525-3544
MicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes. 相似文献
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Pascale Romby Emmanuelle Charpentier 《Cellular and molecular life sciences : CMLS》2010,67(2):217-237
During the last decade, RNA molecules with regulatory functions on gene expression have benefited from a renewed interest.
In bacteria, recent high throughput computational and experimental approaches have led to the discovery that 10–20% of all
genes code for RNAs with critical regulatory roles in metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many of these RNAs act
through binding to their target mRNAs while others modulate protein activity or target DNA. The cis-acting RNAs include regulatory regions of mRNAs that can respond to various signals. These RNAs often provide the missing
link between sensing changing conditions in the environment and fine-tuning the subsequent biological responses. Information
on their various functions and modes of action has been well documented for gram-negative bacteria. Here, we summarize the
current knowledge of regulatory RNAs in gram-positive bacteria. 相似文献
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Hairpin RNA: a secondary structure of primary importance 总被引:4,自引:0,他引:4
An RNA hairpin is an essential secondary structure of RNA. It can guide RNA folding, determine interactions in a ribozyme,
protect messenger RNA (mRNA) from degradation, serve as a recognition motif for RNA binding proteins or act as a substrate
for enzymatic reactions. In this review, we have focused on cis-acting RNA hairpins in metazoa, which regulate histone gene expression, mRNA localization and translation. We also review
evolution, mechanism of action and experimental use of trans-acting microRNAs, which are coded by short RNA hairpins. Finally, we discuss the existence and effects of long RNA hairpin
in animals. We show that several proteins previously recognized to play a role in a specific RNA stem-loop function in cis were also linked to RNA silencing pathways where a different type of hairpin acts in trans. Such overlaps indicate that the relationship between certain mechanisms that recognize different types of RNA hairpins is
closer than previously thought.
Received 21 November 2005; received after revision 3 January 2006; accepted 11 January 2006 相似文献
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Müller UF 《Cellular and molecular life sciences : CMLS》2006,63(11):1278-1293
The RNA world hypothesis states that life originated via a system based on RNA genomes and RNA catalysts. Researchers have
been trying to develop such a system since catalytic RNAs (ribozymes) were discovered in 1982. This review summarizes the
recent progress made in that endeavor and outlines the obstacles that remain to be overcome. After giving a short background
on prebiotic chemistry and in vitro evolution, the discussion focuses on the generation of three important components of an RNA world: a sufficient polymerase
ribozyme, self-replicating membrane compartments and ribozymes that are capable of performing basic metabolic processes.
Received 31 January 2006; accepted 15 March 2006 相似文献
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Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily
conserved SET domain and plays a fundamental role in epigenetic regulation of gene activation and silencing in all eukaryotes.
The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET
domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable
insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains,
either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights
into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine
methylation.
Received 10 June 2006; accepted 22 August 2006 相似文献
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The post-transcriptional steps of eukaryotic ribosome biogenesis 总被引:4,自引:0,他引:4
Henras AK Soudet J Gérus M Lebaron S Caizergues-Ferrer M Mougin A Henry Y 《Cellular and molecular life sciences : CMLS》2008,65(15):2334-2359
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Heeyoung Seok Haejeong Lee Eun-Sook Jang Sung Wook Chi 《Cellular and molecular life sciences : CMLS》2018,75(5):797-814
RNA interference (RNAi) has been widely adopted to repress specific gene expression and is easily achieved by designing small interfering RNAs (siRNAs) with perfect sequence complementarity to the intended target mRNAs. Although siRNAs direct Argonaute (Ago), a core component of the RNA-induced silencing complex (RISC), to recognize and silence target mRNAs, they also inevitably function as microRNAs (miRNAs) and suppress hundreds of off-targets. Such miRNA-like off-target repression is potentially detrimental, resulting in unwanted toxicity and phenotypes. Despite early recognition of the severity of miRNA-like off-target repression, this effect has often been overlooked because of difficulties in recognizing and avoiding off-targets. However, recent advances in genome-wide methods and knowledge of Ago–miRNA target interactions have set the stage for properly evaluating and controlling miRNA-like off-target repression. Here, we describe the intrinsic problems of miRNA-like off-target effects caused by canonical and noncanonical interactions. We particularly focus on various genome-wide approaches and chemical modifications for the evaluation and prevention of off-target repression to facilitate the use of RNAi with secured specificity. 相似文献
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The RecQ family of DNA helicases is highly conserved throughout evolution and plays an important role in the maintenance of
genomic stability in all organisms. Mutations in three of the five known family members in humans, BLM, WRN and RECQL4, give rise to disorders that are characterized by predisposition to cancer and premature aging, emphasizing the importance
of studying the RecQ proteins and their cellular activities. Interestingly, three autosomal recessive disorders have been
associated with mutations in the RECQL4 gene: Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes, thus making RECQL4 unique within the RecQ family of DNA
helicases. To date, however, the molecular function of RECQL4 and the possible cellular pathways in which it is involved remain
poorly understood. Here, we present an overview of recent findings in connection with RECQL4 and try to highlight different
directions the field could head, helping to clarify the role of RECQL4 in preventing tumorigenesis and maintenance of genome
integrity in humans.
Received 31 October 2006; received after revision 4 January 2007; accepted 5 February 2007 相似文献
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Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional
gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can
consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic
gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations
with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon
and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for
production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus).
The aim of this article is to review features of functional gene clusters in prokaryotes and eukaryotes and the significance
of clustering for effective function. 相似文献