scholarly journals Establishing RNA-RNA interactions remodels lncRNA structure and promotes PRC2 activity

2021 ◽  
Vol 7 (16) ◽  
pp. eabc9191
Author(s):  
Maggie M. Balas ◽  
Erik W. Hartwick ◽  
Chloe Barrington ◽  
Justin T. Roberts ◽  
Stephen K. Wu ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Apparent Contradiction ◽  
Polycomb Repressive Complex 2 ◽  
Chemical Probing ◽  
Genome Wide ◽  
Multiple Protein ◽  
Catalytic Inhibitor ◽  
Rna Inhibition ◽  
Nuclear Ribonucleoprotein ◽  
Lncrna Hotair

Human Polycomb Repressive Complex 2 (PRC2) catalysis of histone H3 lysine 27 methylation at certain loci depends on long noncoding RNAs (lncRNAs). Yet, in apparent contradiction, RNA is a potent catalytic inhibitor of PRC2. Here, we show that intermolecular RNA-RNA interactions between the lncRNA HOTAIR and its targets can relieve RNA inhibition of PRC2. RNA bridging is promoted by heterogeneous nuclear ribonucleoprotein B1, which uses multiple protein domains to bind HOTAIR regions via multivalent protein-RNA interactions. Chemical probing demonstrates that establishing RNA-RNA interactions changes HOTAIR structure. Genome-wide HOTAIR/PRC2 activity occurs at genes whose transcripts can make favorable RNA-RNA interactions with HOTAIR. We demonstrate that RNA-RNA matches of HOTAIR with target gene RNAs can relieve the inhibitory effect of a single lncRNA for PRC2 activity after B1 dissociation. Our work highlights an intrinsic switch that allows PRC2 activity in specific RNA contexts, which could explain how many lncRNAs work with PRC2.

scholarly journals Establishing RNA-RNA interactions remodels lncRNA structure and promotes PRC2 activity

2020 ◽  
Author(s):  
Maggie M. Balas ◽  
Erik W. Hartwick ◽  
Chloe Barrington ◽  
Justin T. Roberts ◽  
Stephen K. Wu ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Apparent Contradiction ◽  
Polycomb Repressive Complex 2 ◽  
Chemical Probing ◽  
Genome Wide ◽  
Multiple Protein ◽  
Catalytic Inhibitor ◽  
Rna Inhibition ◽  
Nuclear Ribonucleoprotein ◽  
Lncrna Hotair

ABSTRACTHuman Polycomb Repressive Complex 2 (PRC2) catalysis of histone H3 lysine 27 methylation at certain loci depends on long noncoding RNAs (lncRNAs). Yet, in apparent contradiction, RNA is a potent catalytic inhibitor of PRC2. Here we show that intermolecular RNA-RNA interactions between the lncRNA HOTAIR and its targets can relieve RNA inhibition of PRC2. RNA bridging is promoted by heterogenous nuclear ribonucleoprotein B1, which uses multiple protein domains to bind HOTAIR regions via multi-valent protein-RNA interactions. Chemical probing demonstrates that establishing RNA-RNA interactions changes HOTAIR structure. Genome-wide HOTAIR/PRC2 activity occurs at genes whose transcripts can make favorable RNA-RNA interactions with HOTAIR. We demonstrate that RNA-RNA matches of HOTAIR with target gene RNAs can relieve the inhibitory effect of a single lncRNA for PRC2 activity after B1 dissociation. Our work highlights an intrinsic switch that allows PRC2 activity in specific RNA contexts, which could explain how many lncRNAs work with PRC2.

scholarly journals Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mariana G. Ferrarini ◽  
Avantika Lal ◽  
Rita Rebollo ◽  
Andreas J. Gruber ◽  
Andrea Guarracino ◽  
...  
Keyword(s):  
Transposable Element ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Initiation Factor ◽  
Sequence Variant ◽  
The Novel ◽  
Sequencing Data ◽  
Genome Wide ◽  
Respiratory Cells ◽  
Nuclear Ribonucleoprotein

AbstractThe novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

scholarly journals Enhanced sustainable green revolution yield via nitrogen-responsive chromatin modulation in rice

Science ◽  
2020 ◽  
Vol 367 (6478) ◽  
pp. eaaz2046 ◽  
Author(s):  
Kun Wu ◽  
Shuansuo Wang ◽  
Wenzhen Song ◽  
Jianqing Zhang ◽  
Yun Wang ◽  
...  
Keyword(s):  
Nitrogen Use Efficiency ◽  
Green Revolution ◽  
Agricultural Sustainability ◽  
Nitrogen Use ◽  
Polycomb Repressive Complex 2 ◽  
Della Proteins ◽  
Genome Wide ◽  
Use Efficiency ◽  
Low Nitrogen ◽  
Cereal Yields

Because environmentally degrading inorganic fertilizer use underlies current worldwide cereal yields, future agricultural sustainability demands enhanced nitrogen use efficiency. We found that genome-wide promotion of histone H3 lysine 27 trimethylation (H3K27me3) enables nitrogen-induced stimulation of rice tillering: APETALA2-domain transcription factor NGR5 (NITROGEN-MEDIATED TILLER GROWTH RESPONSE 5) facilitates nitrogen-dependent recruitment of polycomb repressive complex 2 to repress branching-inhibitory genes via H3K27me3 modification. NGR5 is a target of gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1)–promoted proteasomal destruction. DELLA proteins (characterized by the presence of a conserved aspartate-glutamate-leucine-leucine-alanine motif) competitively inhibit the GID1-NGR5 interaction and explain increased tillering of green revolution varieties. Increased NGR5 activity consequently uncouples tillering from nitrogen regulation, boosting rice yield at low nitrogen fertilization levels. NGR5 thus enables enhanced nitrogen use efficiency for improved future agricultural sustainability and food security.

scholarly journals Gene Silencing Triggers Polycomb Repressive Complex 2 Recruitment to CpG Islands Genome Wide

2014 ◽  
Vol 55 (3) ◽  
pp. 347-360 ◽  
Author(s):  
Eva Madi Riising ◽  
Itys Comet ◽  
Benjamin Leblanc ◽  
Xudong Wu ◽  
Jens Vilstrup Johansen ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cpg Islands ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Genome Wide

Polycomb repressive complex 2 coordinates with Sin3 histone deacetylase complex to epigenetically reprogram genome-wide expression of effectors and regulate pathogenicity in Magnaporthe oryzae

2021 ◽  
Author(s):  
Zhongling Wu ◽  
Jiehua Qiu ◽  
Huanbin Shi ◽  
Chuyu Lin ◽  
Jiangnan Yue ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Growth Stage ◽  
Invasive Growth ◽  
Polycomb Repressive Complex ◽  
Host Environment ◽  
Polycomb Repressive Complex 2 ◽  
Genome Wide ◽  
Genome Wide Expression

The strict suppression and reprogramming of gene expression are necessary at different development stages and/or in response to environment stimuli in eukaryotes. In Rice Magnaporthe oryzae pathosystem, effectors from pathogen are kept transcriptionally silenced in the vegetative growth stage and are highly expressed during invasive growth stage to adapt to the host environment. However, the mechanism of how such effectors are stably repressed in the vegetative stage and its roles during rice blast infection remain unclear so far. Here, we showed that all subunits of Polycomb Repressive Complex 2 are required for such repression by direct H3K27me3 occupancy and pathogenic process in M. oryzae. Suppression of polycomb-mediated H3K27me3 causes an improper induction of effectors during vegetative growth thus simulating a host environment. Notably, the addition subunit P55 not only acts as the bridge to connect with core subunits to form a complex in M. oryzae, but also recruits Sin3 histone deacetylase complex to prompt H3K27me3 occupancy for stable maintenance of transcriptional silencing of the target genes in the absence of PRC1. In contrast, during invasive growth stage, the repressed state of effectors chromatin can be partially erased during pathogenic development resulting in transcriptional activation of effectors therein. Overall, Polycomb repressive complex 2 coordinates with Sin3 histone deacetylase complex to epigenetically reprogram genome-wide expression of effectors, which act as molecular switch to memorize the host environment from vegetative to invasive growth, thus contributing to the infection of rice blast.

scholarly journals Genome-wide identification of Arabidopsis non-AUG-initiated upstream ORFs with evolutionarily conserved regulatory sequences that control protein expression levels

2021 ◽  
Author(s):  
Yuta Hiragori ◽  
Hiro Takahashi ◽  
Noriya Hayashi ◽  
Shun Sasaki ◽  
Kodai Nakao ◽  
...  
Keyword(s):  
Regulatory Peptides ◽  
Inhibitory Effect ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Regulatory Sequences ◽  
Dependent Manner ◽  
Protein Coding ◽  
Genome Wide ◽  
Evolutionarily Conserved ◽  
Upstream Open Reading Frames

Upstream open reading frames (uORFs) are short ORFs found in the 5′-UTRs of many eukaryotic transcripts and can influence the translation of protein-coding main ORFs (mORFs). Recent genome-wide ribosome profiling studies have revealed that thousands of uORFs initiate translation at non-AUG start codons. However, the physiological significance of these non-AUG uORFs has so far been demonstrated for only a few of them. It is conceivable that physiologically important non-AUG uORFs are evolutionarily conserved across species. In this study, using a combination of bioinformatics and experimental approaches, we searched the Arabidopsis genome for non-AUG-initiated uORFs with conserved sequences that control the expression of the mORF-encoded proteins. As a result, we identified four novel regulatory non-AUG uORFs. Among these, two exerted repressive effects on mORF expression in an amino acid sequence-dependent manner. These two non-AUG uORFs are likely to encode regulatory peptides that cause ribosome stalling, thereby enhancing their repressive effects. In contrast, one of the identified regulatory non-AUG uORFs promoted mORF expression by alleviating the inhibitory effect of a downstream AUG-initiated uORF. These findings provide insights into the mechanisms that enable non-AUG uORFs to play regulatory roles despite their low translation initiation efficiencies.

scholarly journals RedChIP identifies noncoding RNAs associated with genomic sites occupied by Polycomb and CTCF proteins

2021 ◽  
Vol 119 (1) ◽  
pp. e2116222119
Author(s):  
Alexey A. Gavrilov ◽  
Rinat I. Sultanov ◽  
Mikhail D. Magnitov ◽  
Aleksandra A. Galitsyna ◽  
Erdem B. Dashinimaev ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Binding Sites ◽  
Wide Spectrum ◽  
Noncoding Rnas ◽  
Ctcf Binding ◽  
Polycomb Repressive Complex 2 ◽  
Proximity Ligation ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Architectural Protein

Nuclear noncoding RNAs (ncRNAs) are key regulators of gene expression and chromatin organization. The progress in studying nuclear ncRNAs depends on the ability to identify the genome-wide spectrum of contacts of ncRNAs with chromatin. To address this question, a panel of RNA–DNA proximity ligation techniques has been developed. However, neither of these techniques examines proteins involved in RNA–chromatin interactions. Here, we introduce RedChIP, a technique combining RNA–DNA proximity ligation and chromatin immunoprecipitation for identifying RNA–chromatin interactions mediated by a particular protein. Using antibodies against architectural protein CTCF and the EZH2 subunit of the Polycomb repressive complex 2, we identify a spectrum of cis- and trans-acting ncRNAs enriched at Polycomb- and CTCF-binding sites in human cells, which may be involved in Polycomb-mediated gene repression and CTCF-dependent chromatin looping. By providing a protein-centric view of RNA–DNA interactions, RedChIP represents an important tool for studies of nuclear ncRNAs.

scholarly journals Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells

2013 ◽  
Vol 14 (8) ◽  
pp. R91 ◽  
Author(s):  
Francesco Neri ◽  
Danny Incarnato ◽  
Anna Krepelova ◽  
Stefania Rapelli ◽  
Andrea Pagnani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Polycomb Repressive Complex ◽  
Functional Association ◽  
Polycomb Repressive Complex 2 ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals Arabidopsis spliceosome factor SmD3 modulates immunity to Pseudomonas syringae infection

2021 ◽  
Author(s):  
Anna Golisz ◽  
Michal Krzyszton ◽  
Monika Stepien ◽  
Jakub Dolata ◽  
Justyna Piotrowska ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Plant Immunity ◽  
Mrna Splicing ◽  
Mrna Levels ◽  
Stomatal Development ◽  
Callose Deposition ◽  
Small Nuclear Ribonucleoprotein ◽  
Genome Wide ◽  
Nuclear Ribonucleoprotein

SmD3 is a core component of the small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. The role of Arabidopsis SmD3 in plant immunity was assessed by testing sensitivity of smd3a and smd3b mutants to Pseudomonas syringae pv. tomato (Pst) DC3000 infection and its pathogenesis effectors flagellin (flg22), EF-Tu (elf18) and coronatine (COR). Both smd3 mutants exhibited enhanced susceptibility to Pst accompanied by marked changes in the expression of key pathogenesis markers. mRNA levels of these factors were also altered upon treatment with Pseudomonas effectors. We showed that SmD3-b dysfunction impairs mainly stomatal immunity as a result of defects in stomatal development. Our genome-wide transcriptome analysis of the smd3b-1 mutant infected with Pst revealed that lack of SmD3-b deregulates defense against Pst infection at the transcriptional and posttranscriptional levels including defects in splicing and an altered pattern of alternative splicing. Other changes in the smd3b-1 mutant involved enhanced elf18- and flg22-induced callose deposition, reduction of flg22-triggered production of early ROS and boost of secondary ROS caused by Pst infection. Together, our data indicate that SmD3 contributes to the plant immune response possibly via regulation of mRNA splicing of key pathogenesis factors.

scholarly journals Arabidopsis Spliceosome Factor SmD3 Modulates Immunity to Pseudomonas syringae Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Golisz ◽  
Michal Krzyszton ◽  
Monika Stepien ◽  
Jakub Dolata ◽  
Justyna Piotrowska ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Plant Immunity ◽  
Mrna Splicing ◽  
Mrna Levels ◽  
Stomatal Development ◽  
Response Factors ◽  
Callose Deposition ◽  
Small Nuclear Ribonucleoprotein ◽  
Genome Wide ◽  
Nuclear Ribonucleoprotein

SmD3 is a core component of the small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. The role of Arabidopsis SmD3 in plant immunity was assessed by testing sensitivity of smd3a and smd3b mutants to Pseudomonas syringae pv. tomato (Pst) DC3000 infection and its pathogenesis effectors flagellin (flg22), EF-Tu (elf18) and coronatine (COR). Both smd3 mutants exhibited enhanced susceptibility to Pst accompanied by marked changes in the expression of key pathogenesis markers. mRNA levels of major biotic stress response factors were also altered upon treatment with Pseudomonas effectors. Our genome-wide transcriptome analysis of the smd3b-1 mutant infected with Pst, verified by northern and RT-qPCR, showed that lack of SmD3-b protein deregulates defense against Pst infection at the transcriptional and posttranscriptional levels including defects in splicing and an altered pattern of alternative splicing. Importantly, we show that SmD3-b dysfunction impairs mainly stomatal immunity as a result of defects in stomatal development. We propose that it is the malfunction of the stomata that is the primary cause of an altered mutant response to the pathogen. Other changes in the smd3b-1 mutant involved enhanced elf18- and flg22-induced callose deposition, reduction of flg22-triggered production of early ROS and boost of secondary ROS caused by Pst infection. Together, our data indicate that SmD3 contributes to the plant immune response possibly via regulation of mRNA splicing of key pathogenesis factors.

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