RESUMEN
Faithful transfer of parental histones to newly replicated daughter DNA strands is critical for inheritance of epigenetic states. Although replication proteins that facilitate parental histone transfer have been identified, how intact histone H3-H4 tetramers travel from the front to the back of the replication fork remains unknown. Here, we use AlphaFold-Multimer structural predictions combined with biochemical and genetic approaches to identify the Mrc1/CLASPIN subunit of the replisome as a histone chaperone. Mrc1 contains a conserved histone-binding domain that forms a brace around the H3-H4 tetramer mimicking nucleosomal DNA and H2A-H2B histones, is required for heterochromatin inheritance, and promotes parental histone recycling during replication. We further identify binding sites for the FACT histone chaperone in Swi1/TIMELESS and DNA polymerase α that are required for heterochromatin inheritance. We propose that Mrc1, in concert with FACT acting as a mobile co-chaperone, coordinates the distribution of parental histones to newly replicated DNA.
RESUMEN
CSR-1 is a germline-expressed C. elegans Argonaute protein essential for viability. In this issue of Cell, Gerson-Gurwitz et al. now demonstrate a role for CSR-1 and its slicer activity in downregulating the levels of maternally deposited mRNAs to fine-tune the expression of proteins with critical roles in embryonic cell divisions.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Animales , Proteínas Argonautas/metabolismo , Células Germinativas/metabolismoRESUMEN
Epigenetic inheritance of heterochromatin requires DNA-sequence-independent propagation mechanisms, coupling to RNAi, or input from DNA sequence, but how DNA contributes to inheritance is not understood. Here, we identify a DNA element (termed "maintainer") that is sufficient for epigenetic inheritance of pre-existing histone H3 lysine 9 methylation (H3K9me) and heterochromatin in Schizosaccharomyces pombe but cannot establish de novo gene silencing in wild-type cells. This maintainer is a composite DNA element with binding sites for the Atf1/Pcr1 and Deb1 transcription factors and the origin recognition complex (ORC), located within a 130-bp region, and can be converted to a silencer in cells with lower rates of H3K9me turnover, suggesting that it participates in recruiting the H3K9 methyltransferase Clr4/Suv39h. These results suggest that, in the absence of RNAi, histone H3K9me is only heritable when it can collaborate with maintainer-associated DNA-binding proteins that help recruit the enzyme responsible for its epigenetic deposition.
Asunto(s)
Ensamble y Desensamble de Cromatina , Metilación de ADN , ADN de Hongos/genética , Herencia , Heterocromatina/genética , Secuencias Reguladoras de Ácidos Nucleicos , Schizosaccharomyces/genética , Factores de Transcripción Activadores/genética , Factores de Transcripción Activadores/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Sitios de Unión , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , ADN de Hongos/metabolismo , Epigénesis Genética , Regulación Fúngica de la Expresión Génica , Heterocromatina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/genética , Histonas/metabolismo , Complejo de Reconocimiento del Origen/genética , Complejo de Reconocimiento del Origen/metabolismo , Proteínas/genética , Proteínas/metabolismo , Interferencia de ARN , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismoRESUMEN
Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) are histone-modifying and -binding complexes that mediate the formation of facultative heterochromatin and are required for silencing of developmental genes and maintenance of cell fate1-3. Multiple pathways of RNA decay work together to establish and maintain heterochromatin in fission yeast, including a recently identified role for a conserved RNA-degradation complex known as the rixosome or RIX1 complex4-6. Whether RNA degradation also has a role in the stability of mammalian heterochromatin remains unknown. Here we show that the rixosome contributes to silencing of many Polycomb targets in human cells. The rixosome associates with human PRC complexes and is enriched at promoters of Polycomb target genes. Depletion of either the rixosome or Polycomb results in accumulation of paused and elongating RNA polymerase at Polycomb target genes. We identify point mutations in the RING1B subunit of PRC1 that disrupt the interaction between PRC1 and the rixosome and result in diminished silencing, suggesting that direct recruitment of the rixosome to chromatin is required for silencing. Finally, we show that the RNA endonuclease and kinase activities of the rixosome and the downstream XRN2 exoribonuclease, which degrades RNAs with 5' monophosphate groups generated by the rixosome, are required for silencing. Our findings suggest that rixosomal degradation of nascent RNA is conserved from fission yeast to human, with a primary role in RNA degradation at facultative heterochromatin in human cells.
Asunto(s)
Silenciador del Gen , Heterocromatina , Complejo Represivo Polycomb 1 , Estabilidad del ARN , Exorribonucleasas/genética , Heterocromatina/genética , Humanos , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 2/genética , Proteínas del Grupo Polycomb/genética , Schizosaccharomyces/genéticaRESUMEN
Spatially and functionally distinct domains of heterochromatin and euchromatin play important roles in the maintenance of chromosome stability and regulation of gene expression, but a comprehensive knowledge of their composition is lacking. Here, we develop a strategy for the isolation of native Schizosaccharomyces pombe heterochromatin and euchromatin fragments and analyze their composition by using quantitative mass spectrometry. The shared and euchromatin-specific proteomes contain proteins involved in DNA and chromatin metabolism and in transcription, respectively. The heterochromatin-specific proteome includes all proteins with known roles in heterochromatin formation and, in addition, is enriched for subsets of nucleoporins and inner nuclear membrane (INM) proteins, which associate with different chromatin domains. While the INM proteins are required for the integrity of the nucleolus, containing ribosomal DNA repeats, the nucleoporins are required for aggregation of heterochromatic foci and epigenetic inheritance. The results provide a comprehensive picture of heterochromatin-associated proteins and suggest a role for specific nucleoporins in heterochromatin function.
Asunto(s)
Núcleo Celular/metabolismo , Ensamble y Desensamble de Cromatina/fisiología , Cromatina/metabolismo , Heterocromatina/metabolismo , ADN Ribosómico/metabolismo , Epigénesis Genética/fisiología , Eucromatina/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Proteómica/métodos , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Transcripción Genética/fisiologíaRESUMEN
In this issue of Cell, Rajasethupathy et al. report a surprising role for piRNAs, previously thought to act mainly in the animal germline to silence transposons, in transcriptional regulation of plasticity-related genes in the central nervous system of the sea slug Aplysia californica. The findings expand the functions of small RNAs and have important implications for our understanding of how transient signals can give rise to long-term memories.
RESUMEN
Mechanisms enabling genetically identical cells to differentially regulate gene expression are complex and central to organismal development and evolution. While gene silencing pathways involving DNA sequence-specific recruitment of histone-modifying enzymes are prevalent in nature, examples of sequence-independent heritable gene silencing are scarce. Studies of the fission yeast Schizosaccharomyces pombe indicate that sequence-independent propagation of heterochromatin can occur but requires numerous multisubunit protein complexes and their diverse activities. Such complexity has so far precluded a coherent articulation of the minimal requirements for heritable gene silencing by conventional in vitro reconstitution approaches. Here, we take an unconventional approach to defining these requirements by engineering sequence-independent silent chromatin inheritance in budding yeast Saccharomyces cerevisiae cells. The mechanism conferring memory upon these cells is remarkably simple and requires only two proteins, one that recognizes histone H3 lysine 9 methylation (H3K9me) and catalyzes the deacetylation of histone H4 lysine 16 (H4K16), and another that recognizes deacetylated H4K16 and catalyzes H3K9me. Together, these bilingual "read-write" proteins form an interdependent positive feedback loop that is sufficient for the transmission of DNA sequence-independent silent information over multiple generations.
Asunto(s)
Cromatina , Lisina , Cromatina/genética , Histonas/genética , Heterocromatina/genética , Silenciador del GenRESUMEN
Studies in eukaryotes ranging from yeast to mammals indicate that specific chromatin structures can be inherited following DNA replication via mechanisms acting in cis. Both the initial establishment of such chromatin structures and their inheritance require sequence-dependent specificity factors and changes in histone posttranslational modifications. Here I propose models for the maintenance of epigenetic information in which DNA silencers or nascent RNA scaffolds act as sensors that work cooperatively with parentally inherited histones to re-establish chromatin states following DNA replication.
Asunto(s)
Cromatina/metabolismo , Epigénesis Genética , Animales , Células Eucariotas/metabolismo , Código de Histonas , HumanosRESUMEN
Assembly of fission yeast pericentromeric heterochromatin and generation of small interfering RNAs (siRNAs) from noncoding centromeric transcripts are mutually dependent processes. How this interdependent positive feedback loop is first triggered is a fundamental unanswered question. Here, we show that two distinct Argonaute (Ago1)-dependent pathways mediate small RNA generation. RNA-dependent RNA polymerase complex (RDRC) and Dicer act on specific noncoding RNAs to generate siRNAs by a mechanism that requires the slicer activity of Ago1 but is independent of pre-existing heterochromatin. In the absence of RDRC or Dicer, a distinct class of small RNAs, called primal small RNAs (priRNAs), associates with Ago1. priRNAs are degradation products of abundant transcripts, which bind to Ago1 and target antisense transcripts that result from bidirectional transcription of DNA repeats. Our results suggest that a transcriptome surveillance mechanism based on random association of RNA degradation products with Argonaute triggers siRNA amplification and heterochromatin assembly within DNA repeats.
Asunto(s)
Heterocromatina/metabolismo , Interferencia de ARN , Schizosaccharomyces/metabolismo , Proteínas Argonautas , Centrómero/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Modelos Genéticos , ARN/metabolismo , Procesamiento de Término de ARN 3' , ARN Nucleotidiltransferasas/metabolismo , Estabilidad del ARN , ARN sin Sentido/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas de Unión al ARN/metabolismo , ARN Polimerasa Dependiente del ARN/metabolismo , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Transcripción GenéticaRESUMEN
Two recent papers (Larson et al., 2017; Strom et al., 2017) in Nature propose that heterochromatic domains are organized into phase-separated liquid compartments. Here we highlight the main findings that support the liquid-like nature of HP1 domains and discuss their functional implications in gene silencing and genome organization.
Asunto(s)
Proteínas Cromosómicas no Histona/genética , Heterocromatina , Silenciador del GenRESUMEN
In animal cells, small RNA molecules, called piRNAs, defend the genome against selfish DNA elements such as transposons. In this issue, Klattenhoff et al. (2009) report that an HP1 family protein, Rhino, is required for piRNA generation and transposon silencing in Drosophila germline cells. The results provide a link between heterochromatin and piRNA-mediated genome defense.
Asunto(s)
Elementos Transponibles de ADN , Drosophila melanogaster/genética , Silenciador del Gen , ARN Interferente Pequeño/metabolismo , Animales , Drosophila melanogaster/metabolismo , Genoma de los InsectosRESUMEN
Heterochromatin plays a key role in protection of chromosome integrity by suppressing homologous recombination. In Saccharomyces cerevisiae, Sir2p, Sir3p, and Sir4p are structural components of heterochromatin found at telomeres and the silent mating-type loci. Here we have investigated whether incorporation of Sir proteins into minichromosomes regulates early steps of recombinational repair in vitro. We find that addition of Sir3p to a nucleosomal substrate is sufficient to eliminate yRad51p-catalyzed formation of joints, and that this repression is enhanced by Sir2p/Sir4p. Importantly, Sir-mediated repression requires histone residues that are critical for silencing in vivo. Moreover, we demonstrate that the SWI/SNF chromatin-remodeling enzyme facilitates joint formation by evicting Sir3p, thereby promoting subsequent Rad54p-dependent formation of a strand invasion product. These results suggest that recombinational repair in the context of heterochromatin presents additional constraints that can be overcome by ATP-dependent chromatin-remodeling enzymes.
Asunto(s)
Adenosina Trifosfato/metabolismo , Ensamble y Desensamble de Cromatina , Reparación del ADN , Heterocromatina/metabolismo , Recombinación Genética , Proteínas Cromosómicas no Histona/metabolismo , Histona Desacetilasas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas Reguladoras de Información Silente de Saccharomyces cerevisiae/metabolismo , Sirtuina 2 , Sirtuinas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression1,2. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs3-7. RNA interference (RNAi)-mediated histone H3 lysine 9 methylation (H3K9me) and heterochromatin formation define a potential epigenetic inheritance mechanism in which positive feedback involving short interfering RNA (siRNA) amplification can be directly coupled to histone PTM positive feedback8-14. However, it is not known whether the coupling of these two feedback loops can maintain epigenetic silencing independently of DNA sequence and in the absence of enabling mutations that disrupt genome-wide chromatin structure or transcription15-17. Here, using the fission yeast Schizosaccharomyces pombe, we show that siRNA-induced H3K9me and silencing of a euchromatic gene can be epigenetically inherited in cis during multiple mitotic and meiotic cell divisions in wild-type cells. This inheritance involves the spreading of secondary siRNAs and H3K9me3 to the targeted gene and surrounding areas, and requires both RNAi and H3K9me, suggesting that the siRNA and H3K9me positive-feedback loops act synergistically to maintain silencing. By contrast, when maintained solely by histone PTM positive feedback, silencing is erased by H3K9 demethylation promoted by Epe1, or by interallelic interactions that occur after mating to cells containing an expressed allele even in the absence of Epe1. These findings demonstrate that the RNAi machinery can mediate transgenerational epigenetic inheritance independently of DNA sequence or enabling mutations, and reveal a role for the coupling of the siRNA and H3K9me positive-feedback loops in the protection of epigenetic alleles from erasure.
Asunto(s)
Histonas/metabolismo , Lisina/metabolismo , Metilación , Interferencia de ARN , Schizosaccharomyces/genética , Alelos , Proteínas de Ciclo Celular/genética , Epigenómica , Retroalimentación Fisiológica , Genes Fúngicos/genética , Heterocromatina/genética , Heterocromatina/metabolismo , N-Metiltransferasa de Histona-Lisina , Metiltransferasas/genética , Proteínas Nucleares/genética , Schizosaccharomyces/citología , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genéticaRESUMEN
Histone H3 lysine 9 methylation (H3K9me) mediates heterochromatic gene silencing and is important for genome stability and the regulation of gene expression1-4. The establishment and epigenetic maintenance of heterochromatin involve the recruitment of H3K9 methyltransferases to specific sites on DNA, followed by the recognition of pre-existing H3K9me by the methyltransferase and methylation of proximal histone H35-11. This positive feedback loop must be tightly regulated to prevent deleterious epigenetic gene silencing. Extrinsic anti-silencing mechanisms involving histone demethylation or boundary elements help to limit the spread of inappropriate H3K9me12-15. However, how H3K9 methyltransferase activity is locally restricted or prevented from initiating random H3K9me-which would lead to aberrant gene silencing and epigenetic instability-is not fully understood. Here we reveal an autoinhibited conformation in the conserved H3K9 methyltransferase Clr4 (also known as Suv39h) of the fission yeast Schizosaccharomyces pombe that has a critical role in preventing aberrant heterochromatin formation. Biochemical and X-ray crystallographic data show that an internal loop in Clr4 inhibits the catalytic activity of this enzyme by blocking the histone H3K9 substrate-binding pocket, and that automethylation of specific lysines in this loop promotes a conformational switch that enhances the H3K9me activity of Clr4. Mutations that are predicted to disrupt this regulation lead to aberrant H3K9me, loss of heterochromatin domains and inhibition of growth, demonstrating the importance of the intrinsic inhibition and auto-activation of Clr4 in regulating the deposition of H3K9me and in preventing epigenetic instability. Conservation of the Clr4 autoregulatory loop in other H3K9 methyltransferases and the automethylation of a corresponding lysine in the human SUV39H2 homologue16 suggest that the mechanism described here is broadly conserved.
Asunto(s)
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Epigénesis Genética , Histona Metiltransferasas/química , Histona Metiltransferasas/metabolismo , Histonas/metabolismo , Metiltransferasas/química , Metiltransferasas/metabolismo , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimología , Schizosaccharomyces/genética , Evolución Molecular , Silenciador del Gen , Heterocromatina/química , Heterocromatina/genética , Heterocromatina/metabolismo , N-Metiltransferasa de Histona-Lisina/química , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/química , Humanos , Metilación , Conformación ProteicaRESUMEN
Small-RNA (sRNA)-guided transcriptional gene silencing by Argonaute (Ago)-containing complexes is fundamental to genome integrity and epigenetic inheritance. The RNA cleavage ("Slicer") activity of Argonaute has been implicated in both sRNA maturation and target RNA cleavage. Typically, Argonaute slices and releases the passenger strand of duplex sRNA to generate active silencing complexes, but it remains unclear whether slicing of target nascent RNAs, or other RNAi components, also contributes to downstream transcriptional silencing. Here, we develop a strategy for loading the fission yeast Ago1 with a single-stranded sRNA guide, which bypasses the requirement for slicer activity in generation of active silencing complexes. We show that slicer-defective Ago1 can mediate secondary sRNA generation, H3K9 methylation, and silencing similar to or better than wild-type and associates with chromatin more efficiently. The results define an ancient and minimal sRNA-mediated chromatin silencing mechanism, which resembles the germline-specific sRNA-dependent transcriptional silencing pathways in Drosophila and mammals.
Asunto(s)
Proteínas Argonautas/metabolismo , Ensamble y Desensamble de Cromatina , Heterocromatina/metabolismo , Interferencia de ARN , ARN de Hongos/metabolismo , ARN Interferente Pequeño/biosíntesis , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimología , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Proteínas Argonautas/genética , Metilación de ADN , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Regulación Fúngica de la Expresión Génica , Histonas/metabolismo , ARN de Hongos/genética , ARN Interferente Pequeño/genética , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Transcripción GenéticaRESUMEN
Heterochromatic DNA domains have important roles in the regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway. Typically, sRNAs, originating from long noncoding RNAs, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and trimethylation (H3K9me2 and H3K9me3, respectively) and the formation of heterochromatin. H3K9me is in turn required for the recruitment of RNAi to chromatin to promote the amplification of sRNA. Yet, how heterochromatin formation, which silences transcription, can proceed by a co-transcriptional mechanism that also promotes sRNA generation remains paradoxical. Here, using Clr4, the fission yeast Schizosaccharomyces pombe homologue of mammalian SUV39H H3K9 methyltransferases, we design active-site mutations that block H3K9me3, but allow H3K9me2 catalysis. We show that H3K9me2 defines a functionally distinct heterochromatin state that is sufficient for RNAi-dependent co-transcriptional gene silencing at pericentromeric DNA repeats. Unlike H3K9me3 domains, which are transcriptionally silent, H3K9me2 domains are transcriptionally active, contain modifications associated with euchromatic transcription, and couple RNAi-mediated transcript degradation to the establishment of H3K9me domains. The two H3K9me states recruit reader proteins with different efficiencies, explaining their different downstream silencing functions. Furthermore, the transition from H3K9me2 to H3K9me3 is required for RNAi-independent epigenetic inheritance of H3K9me domains. Our findings demonstrate that H3K9me2 and H3K9me3 define functionally distinct chromatin states and uncover a mechanism for the formation of transcriptionally permissive heterochromatin that is compatible with its broadly conserved role in sRNA-mediated genome defence.
Asunto(s)
Silenciador del Gen , Heterocromatina/genética , Heterocromatina/metabolismo , Histonas/química , Histonas/metabolismo , Interferencia de ARN , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Transcripción Genética , Secuencia de Aminoácidos , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Silenciador del Gen/efectos de los fármacos , Heterocromatina/química , N-Metiltransferasa de Histona-Lisina , Ácidos Hidroxámicos/farmacología , Metilación/efectos de los fármacos , Metiltransferasas/metabolismo , Mutación , Proteínas Represoras/metabolismo , Schizosaccharomyces/efectos de los fármacos , Proteínas de Schizosaccharomyces pombe/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
Non-random positioning of chromosomal domains relative to each other and to nuclear landmarks is a common feature of eukaryotic genomes. In particular, the distribution of DNA loci relative to the nuclear periphery has been linked to both transcriptional activation and repression. Nuclear pores and other integral membrane protein complexes are key players in the dynamic organization of the genome in the nucleus, and recent advances in our understanding of the molecular networks that organize genomes at the nuclear periphery point to a further role for non-random locus positioning in DNA repair, recombination and stability.
Asunto(s)
Regulación de la Expresión Génica , Genoma/genética , Inestabilidad Genómica , Membrana Nuclear/metabolismo , Animales , Citoesqueleto/metabolismo , ADN/metabolismo , HumanosRESUMEN
Endogenous small interfering RNAs (siRNAs) and other classes of small RNA provide the specificity signals for silencing of transposons and repeated DNA elements at the posttranscriptional and transcriptional levels. However, the determinants that define an siRNA-producing region or control the silencing function of siRNAs are poorly understood. Here we show that convergent antisense transcription and availability of the Dicer ribonuclease are the key determinants for primary siRNA generation. Surprisingly, Dicer makes dual contributions to heterochromatin formation, promoting histone H3 lysine 9 methylation independently of its catalytic activity, in addition to its well-known role in catalyzing siRNA generation. Furthermore, sequences in the 3' UTR of an mRNA-coding gene inhibit the ability of siRNAs to promote heterochromatin formation, providing another layer of control that prevents the silencing of protein-coding RNAs. Our results reveal distinct mechanisms that limit siRNA generation to centromeric DNA repeats and prevent spurious siRNA-mediated silencing at euchromatic loci.
Asunto(s)
Heterocromatina/metabolismo , ARN Interferente Pequeño/fisiología , Schizosaccharomyces/genética , Endorribonucleasas/metabolismo , Endorribonucleasas/fisiología , Regulación de la Expresión Génica , Histonas/metabolismo , Metilación , Poliadenilación , Señales de Poliadenilación de ARN 3' , Interferencia de ARN , Procesamiento Postranscripcional del ARN , ARN Interferente Pequeño/biosíntesis , ARN Interferente Pequeño/metabolismo , Ribonucleasa III/metabolismo , Ribonucleasa III/fisiología , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/fisiologíaRESUMEN
Diverse classes of RNA, ranging from small to long non-coding RNAs, have emerged as key regulators of gene expression, genome stability and defence against foreign genetic elements. Small RNAs modify chromatin structure and silence transcription by guiding Argonaute-containing complexes to complementary nascent RNA scaffolds and then mediating the recruitment of histone and DNA methyltransferases. In addition, recent advances suggest that chromatin-associated long non-coding RNA scaffolds also recruit chromatin-modifying complexes independently of small RNAs. These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.
Asunto(s)
Ensamble y Desensamble de Cromatina/fisiología , Epigénesis Genética/genética , Regulación de la Expresión Génica/genética , Modelos Biológicos , Interferencia de ARN , ARN/metabolismo , Arabidopsis , Metilación de ADN , Silenciador del Gen , Heterocromatina/fisiología , ARN/genética , ARN Interferente Pequeño/metabolismo , LevadurasRESUMEN
RNAi in Schizosaccharomyces pombe is critical for centromeric heterochromatin formation. It has remained unclear, however, whether RNAi also regulates the expression of protein-coding loci. In the April 1, 2012, issue of Genes & Development, Woolcock and colleagues (pp. 683-667) reported an elegant mechanism for the conditional RNAi-mediated repression of stress response genes involving association with Dcr1 at the nuclear pore. Unexpectedly, the initial targeting of RNAi components to these genes does not require small RNA guides.