Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast

Buker, Shane M.; Iida, Tetsushi; Bühler, Marc; Villén, Judit; Gygi, Steven P.; Nakayama, Jun‐ichi; Moazed, Danesh

doi:10.1038/nsmb1211

Cited by 108 publications

(156 citation statements)

References 45 publications

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“…Not applicable DNA elimination scnRNAs, siRNA Lee and Collins, 2006) N. crassa (2) Qde2* Not applicable Quelling siRNA (Catalanotto et al, 2002;Maiti et al, 2007) S. pombe (1) Ago1* Not applicable Heterochromatic silencing, hcRNA (Irvine et al, 2006;Buker et al, 2007) chromosome segregation…”

Section: Twi1mentioning

confidence: 99%

The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members

2008

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Several distinct classes of small RNAs, some newly identified, have been discovered to play important regulatory roles in diverse cellular processes. These classes include siRNAs, miRNAs, rasiRNAs and piRNAs. Each class binds to distinct members of the Argonaute/Piwi protein family to form ribonucleoprotein complexes that recognize partially, or nearly perfect,complementary nucleic acid targets, and that mediate a variety of regulatory processes, including transcriptional and post-transcriptional gene silencing. Based on the known relationship of Argonaute/Piwi proteins with distinct classes of small RNAs, we can now predict how many new classes of small RNAs or silencing processes remain to be discovered.

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Section: Twi1mentioning

confidence: 99%

The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members

2008

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“…However, by using the Conserved Domain Search service (CD-Search) (26,27), an Arb2 conserved domain was detected in the FAM172A protein sequence. Arb2 is required for histone H3 Lys9 (H3-K9) methylation, heterochromatin assembly and siRNA generation (28). Histone H3 lysine methylation is generally associated with either gene activation or repression depending on the site of methylation (29,30).…”

Section: Discussionmentioning

confidence: 99%

Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells

Dong²,

Leong³

et al. 2010

Int J Mol Med

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Abstract. The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage. IntroductionThe chronic complications of diabetes are generally divided into microvascular and macrovascular complications. The diabetic macrovascular disease or atherosclerosis and its complications, are the leading causes of morbidity and mortality in patients with type 2 diabetes mellitus (1,2). The histopathology of atherosclerosis in patients with diabetes is similar to that in patients without diabetes. However, compared to non-diabetic patients, atherosclerotic vascular damage in diabetic patients is more diffuse, more complicated and with clinically worse outcomes (3). Although insulin resistance, hypertension, dyslipidemia and other risk factors certainly contribute to the progression of diabetic macroangiopathy (3-8), the exact mechanisms of these pathological processes remain to be elucidated.Chronic hyperglycemia is a hallmark characteristic of diabetes and exerts its adverse effects on the cardiovascular system in many ways (7). There is universal agreement that hyperglycemia is a powerful and independent risk factor for diabetic cardiovascular complications (9-13). Therefore, hyperglycemia plays a crucial role in the pathogenesis of diabetic macrovascular complications.Glucose is one of the most important factors by which the expressions of genes in vascular or other cells are regulated. We, as well as others, have previously sugges...

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“…In addition, Ago1 slicing activity is required for TGS (37). A recent study showed the presence of another Ago1 complex, named the argonaute siRNA chaperone (ARC), in S. pombe (38). Interestingly, the slicing activity of Ago1 in this complex is inhibited by a protein partner, Arb1.…”

Section: Molecular Interaction Network Centered On Argonaute Proteinmentioning

confidence: 99%

Phylogenetic Comparison of Small RNA-triggered Transcriptional Gene Silencing

Zhang

Rossi

2011

Journal of Biological Chemistry

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The discovery of RNA interference has revealed complex roles for small RNAs in regulating gene expression and cellular physiology. Small RNAs have been demonstrated to be involved in post-transcriptional suppression of translation, targeted degradation of messenger RNAs, and transcriptional suppression via epigenetic modifications of histones and DNA. In fission yeast, RNAi mediates suppression of centromeric transcripts, whereas in plants, transcriptional gene silencing appears to be primarily an antiviral mechanism. In mammals, the well annotated functional role of RNAi is primarily post-transcriptional, but there is increasing evidence that this mechanism can also work to suppress or modulate gene transcription, although it is not clear what primary function this serves. We overview, compare, and contrast the transcriptional silencing pathways in yeast, plants, and mammals in this article. This minireview is intended to provide the reader with a framework of how the RNAi machinery appears to be universally involved in various aspects of transcriptional regulation with discussions of similarities and differences in the components and mechanisms of achieving transcriptional silencing.The phenomenon of siRNA-triggered transcriptional gene silencing (TGS) 2 is conserved across different phyla. In the fission yeast Schizosaccharomyces pombe, siRNA TGS is associated closely with heterochromatin-related gene silencing (1). In the plant Arabidopsis thaliana, siRNA-mediated TGS is associated with the establishment and maintenance of DNA methylation (RNA-directed DNA methylation) (2). In mammalian cells, studies of siRNA-triggered TGS have thus far focused only on the transcriptional silencing of protein-encoding genes via the application of promoter-targeted siRNAs (3). Although different organisms have developed diversified protein players in this process, some commonly shared features exist, especially the argonaute proteins. In general, the mechanism of siRNA TGS is composed of three mutually related parts: 1) the biogenesis and amplification of siRNA triggers, 2) molecular interactions involving an Argonaute Protein and a noncoding or coding RNA, and 3) the accompanied epigenetic changes such as histone modifications and DNA methylation. Biogenesis and Amplification of siRNA TriggersGenetic studies have contributed to establishing a correlation between RNAi and TGS (1, 2). Post-TGS (PTGS) and TGS share some of the same machinery to produce the siRNA triggers (4). In S. pombe, the major RNAi proteins for siRNA production during PTGS and TGS are identical, including the argonaute protein Ago1, the RNase III enzyme Dicer (Dcr1), and an RNA-dependent RNA polymerase (Rdp1), all of which are derived from single-copy genes (5). In contrast, the plant A. thaliana has developed a more complex system in which the argonaute proteins Ago4 and Ago6, the nuclear Dicer enzyme DCL2-4, and the RNA-dependent RNA polymerase Rdr2 are all required for TGS (6 -9). The siRNA triggers for TGS in plants are mainly 24 nucleotides in leng...

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Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast

Cited by 108 publications

References 45 publications

The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members

The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members

Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells

Phylogenetic Comparison of Small RNA-triggered Transcriptional Gene Silencing

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