A molecular code for splicing silencing: configurations of guanosine-rich motifs

2004 ◽  
Vol 32 (6) ◽  
pp. 924-927 ◽  
Author(s):  
P.J. Grabowski
Keyword(s):  
Transcriptional Level ◽  
Cassette Exon ◽  
Sequence Motifs ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Genome Wide ◽  
Splicing Pattern ◽  
Molecular Determinants ◽  
Nuclear Ribonucleoprotein

Alternative pre-mRNA splicing is frequently used to expand the protein-coding capacity of genomes, and to regulate gene expression at the post-transcriptional level. It is a significant challenge to decipher the molecular language of tissue-specific splicing because the inherent flexibility of these mechanisms is specified by numerous short sequence motifs distributed in introns and exons. In the present study, we employ the glutamate NMDA (N-methyl-D-aspartate) R1 receptor (GRIN1) transcript as a model system to identify the molecular determinants for a brain region-specific exon silencing mechanism. We identify a set of guanosine-rich motifs that function co-operatively to regulate the CI cassette exon in a manner consistent with its in vivo splicing pattern. Whereas hnRNP (heterogeneous nuclear ribonucleoprotein) A1 mediates silencing of the CI cassette exon in conjunction with the guanosine-rich motifs, hnRNP H functions as an antagonist to silencing. Genome-wide analysis shows that, while this motif pattern is rarely present in human and mouse exons, those exons for which the pattern is conserved are generally found to be skipped exons. The identification of a similar arrangement of guanosine-rich motifs in transcripts of the hnRNP H family of splicing factors has implications for their co-ordinate regulation at the level of splicing.

scholarly journals One Small RNA of Fusarium graminearum Targets and Silences CEBiP Gene in Common Wheat

2019 ◽  
Vol 7 (10) ◽  
pp. 425 ◽  
Author(s):  
Jiao Jian ◽  
Xu Liang
Keyword(s):  
Fusarium Graminearum ◽  
Small Rna ◽  
Pathogenic Fungus ◽  
Effective Means ◽  
Transcriptional Level ◽  
Head Blight ◽  
Protein Coding ◽  
Pathogen Invasion

The pathogenic fungus Fusarium graminearum (F. graminearum), causing Fusarium head blight (FHB) or scab, is one of the most important cereal killers worldwide, exerting great economic and agronomic losses on global grain production. To repress pathogen invasion, plants have evolved a sophisticated innate immunity system for pathogen recognition and defense activation. Simultaneously, pathogens continue to evolve more effective means of invasion to conquer plant resistance systems. In the process of co-evolution of plants and pathogens, several small RNAs (sRNAs) have been proved in regulating plant immune response and plant-microbial interaction. In this study, we report that a F. graminearum sRNA (Fg-sRNA1) can suppress wheat defense response by targeting and silencing a resistance-related gene, which codes a Chitin Elicitor Binding Protein (TaCEBiP). Transcriptional level evidence indicates that Fg-sRNA1 can target TaCEBiP mRNA and trigger silencing of TaCEBiP in vivo, and in Nicotiana benthamiana (N. benthamiana) plants, Western blotting experiments and YFP Fluorescence observation proofs show that Fg-sRNA1 can suppress the accumulation of protein coding by TaCEBiP gene in vitro. F. graminearum PH-1 strain displays a weakening ability to invasion when Barley stripe mosaic virus (BSMV) vector induces effective silencing Fg-sRNA1 in PH-1 infected wheat plants. Taken together, our results suggest that a small RNA from F. graminearum can target and silence the wheat TaCEBiP gene to enhance invasion of F. graminearum.

scholarly journals Regulatory Variants and Disease: The E-Cadherin −160C/A SNP as an Example

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Gongcheng Li ◽  
Tiejun Pan ◽  
Dan Guo ◽  
Long-Cheng Li
Keyword(s):  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Regulatory Snps ◽  
E Cadherin

Single nucleotide polymorphisms (SNPs) occurring in noncoding sequences have largely been ignored in genome-wide association studies (GWAS). Yet, amounting evidence suggests that many noncoding SNPs especially those that are in the vicinity of protein coding genes play important roles in shaping chromatin structure and regulate gene expression and, as such, are implicated in a wide variety of diseases. One of such regulatory SNPs (rSNPs) is the E-cadherin (CDH1) promoter −160C/A SNP (rs16260) which is known to affect E-cadherin promoter transcription by displacing transcription factor binding and has been extensively scrutinized for its association with several diseases especially malignancies. Findings from studying this SNP highlight important clinical relevance of rSNPs and justify their inclusion in future GWAS to identify novel disease causing SNPs.

scholarly journals Cell-specific cis-natural antisense transcripts (cis-NATs) in the sperm and the pollen vegetative cells of Arabidopsis thaliana

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 93
Author(s):  
Peng Qin ◽  
Ann E. Loraine ◽  
Sheila McCormick
Keyword(s):  
Gene Expression ◽  
Vegetative Cell ◽  
Cell Types ◽  
Antisense Transcripts ◽  
Vegetative Cells ◽  
Natural Antisense Transcripts ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Genome Wide ◽  
Gene Models

Background: cis-NATs (cis-natural antisense transcripts) are transcribed from opposite strands of adjacent genes and have been shown to regulate gene expression by generating small RNAs from the overlapping region. cis-NATs are important for plant development and resistance to pathogens and stress. Several genome-wide investigations identified a number of cis-NAT pairs, but these investigations predicted cis-NATS using expression data from bulk samples that included lots of cell types. Some cis-NAT pairs identified from those investigations might not be functional, because both transcripts of cis-NAT pairs need to be co-expressed in the same cell. Pollen only contains two cell types, two sperm and one vegetative cell, which makes cell-specific investigation of cis-NATs possible. Methods: We investigated potential protein-coding cis-NATs in pollen and sperm using pollen RNA-seq data and TAIR10 gene models using the Integrated Genome Browser.  We then used sperm microarray data and sRNAs in sperm and pollen to determine possibly functional cis-NATs in the sperm or vegetative cell, respectively. Results: We identified 1471 potential protein-coding cis-NAT pairs, including 131 novel pairs that were not present in TAIR10 gene models. In pollen, 872 possibly functional pairs were identified. 72 and 56 pairs were potentially functional in sperm and vegetative cells, respectively. sRNAs were detected at 794 genes, belonging to 739 pairs. Conclusion: These potential candidates in sperm and the vegetative cell are tools for understanding gene expression mechanisms in pollen.

scholarly journals Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids

2020 ◽  
Vol 21 (6) ◽  
pp. 2001
Author(s):  
Silvia Mercurio ◽  
Silvia Cauteruccio ◽  
Raoul Manenti ◽  
Simona Candiani ◽  
Giorgio Scarì ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Neural Development ◽  
Peptide Nucleic Acids ◽  
Model Organism ◽  
Ciona Intestinalis ◽  
Transcriptional Level ◽  
Regulate Gene Expression

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

scholarly journals Genome-Wide Reconstitution of Chromatin Transactions: RSC Preferentially disrupts H2A.Z-Containing Nucleosomes

2018 ◽  
Author(s):  
Aylin Cakiroglu ◽  
Cedric R. Clapier ◽  
Andreas H. Ehrensberger ◽  
Elodie Darbo ◽  
Bradley R. Cairns ◽  
...  
Keyword(s):  
Experimental System ◽  
Yeast Genome ◽  
Natural Material ◽  
Trna Genes ◽  
Genomic Context ◽  
Protein Coding ◽  
Genome Wide ◽  
Nucleosome Stability

Chromatin transactions are typically studied in vivo, or in vitro using artificial chromatin lacking the epigenetic complexity of the natural material. Attempting to bridge the gap between these approaches, we established a system for isolating the yeast genome as a library of mono-nucleosomes harboring the natural epigenetic signature, suitable for biochemical manipulation. Combined with deep sequencing, this library was used to investigate the intrinsic stability of individual nucleosomes, and – as proof of principle - the nucleosome preference of the chromatin remodeling complex, RSC. Our data indicate that the natural stability of nucleosomes differs greatly, with nucleosomes on tRNA genes and on promoters of protein-coding genes standing out as intrinsically unstable. Interestingly, RSC shows a distinct preference for nucleosomes derived from regions with a high density of histone variant H2A.Z, and this preference is indeed markedly diminished using nucleosomes from cells lacking H2A.Z. Importantly, the preference for H2A.Z remodeling/nucleosome ejection can also be reconstituted with recombinant nucleosome arrays. Together, our data indicate that, despite being separated from their genomic context, individual nucleosomes can retain their original identity as promoter- or TSS-nucleosomes. Besides shedding new light on nucleosome stability and the chromatin remodeler RSC, the simple experimental system outlined here should be generally applicable to the study of chromatin transactions.

Multiple products from microRNA transcripts

2013 ◽  
Vol 41 (4) ◽  
pp. 850-854 ◽  
Author(s):  
Antonio Marco ◽  
Maria Ninova ◽  
Sam Griffiths-Jones
Keyword(s):  
Mirna Precursor ◽  
Open Reading Frames ◽  
Transcriptional Level ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Polycistronic Transcript ◽  
Multiple Products ◽  
Functional Product ◽  
Single Transcript ◽  
Polycistronic Transcripts

A single transcript sometimes codes for more than one product. In bacteria, and in a few exceptional animal lineages, many genes are organized into operons: clusters of open reading frames that are transcribed together in a single polycistronic transcript. However, polycistronic transcripts are rare in eukaryotes. One notable exception is that of miRNAs (microRNAs), small RNAs that regulate gene expression at the post-transcriptional level. The primary transcripts of miRNAs commonly produce more than one functional product, by at least three different mechanisms. miRNAs are often produced from polycistronic transcripts together with other miRNA precursors. Also, miRNAs frequently derive from protein-coding gene introns. Finally, each miRNA precursor can produce two mature miRNA products. We argue, in the present review, that miRNAs are frequently hosted in transcripts coding for multiple products because new miRNA precursor sequences that arise by chance in transcribed regions are more likely to become functional miRNAs during evolution.

scholarly journals Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation

2020 ◽  
Author(s):  
Shiyang Liu ◽  
Nathan Harmston ◽  
Trudy Lee Glaser ◽  
Yunka Wong ◽  
Zheng Zhong ◽  
...  
Keyword(s):  
Cell Growth ◽  
Wnt Signaling ◽  
Cancer Cell ◽  
Cultured Cells ◽  
Cancer Cell Growth ◽  
Protein Coding ◽  
Genome Wide ◽  
Multiple Protein

AbstractBackgroundWnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized.ResultsWe comprehensively mapped lncRNAs from an orthotopic Wnt-addicted pancreatic cancer model, identifying 3,633 lncRNAs, of which 1,503 were regulated by Wnt signaling. We found lncRNAs were much more sensitive to changes in Wnt signaling in xenografts than in cultured cells. To functionally validate Wnt-regulated lncRNAs, we performed CRISPRi screens to assess their role in cancer cell proliferation. Consistent with previous genome-wide lncRNA CRISPRi screens, around 1% (13/1,503) of the Wnt-regulated lncRNAs could modify cancer cell growth in vitro. This included CCAT1 and LINC00263, previously reported to regulate cancer growth. Using an in vivo CRISPRi screen, we doubled the discovery rate, identifying twice as many Wnt-regulated lncRNAs (25/1,503) that had a functional effect on cancer cell growth.ConclusionsOur study demonstrates the value of studying lncRNA functions in vivo, provides a valuable resource of lncRNAs regulated by Wnt signaling and establishes a framework for systematic discovery of functional lncRNAs.

scholarly journals Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development

2021 ◽  
Author(s):  
Chang-Mei Liu ◽  
Shang-Kun Dai ◽  
Pei-Pei Liu ◽  
Zhao-Qian Teng
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Neural Development ◽  
Functional Interpretation ◽  
Regulate Gene Expression ◽  
Cell Fate Decisions ◽  
Histone Lysine ◽  
Genome Wide ◽  
Neural Cell Fate

Metabolites such as crotonyl-CoA and lactyl-CoA influence gene expression through covalently modifying histones, known as histone lysine crotonylation (Kcr) and histone lysine lactylation (Kla). However, we do not know their dynamic changes, biological functions and associations with histone lysine acetylation (Kac) in vivo and during development. Here, we profile H3K9ac, H3K9cr and H3K18la in the developing telencephalon, and find that genome-wide alterations of these histone marks collaboratively regulate transcriptome remodelling to favour neural differentiation. We also demonstrate that global histone Kcr and Kla levels are not affected by transcription inhibition. Importantly, we identify HDAC1-3 as novel erasers of H3K18la and furtherly show that a selective inhibitor of HDAC1-3, MS-275 promotes transcriptional programs associated with neural cell fate decisions via H3K18la. Taken together, our results uncover the interplays between histone lysine acylations to regulate gene expression and the differentiation-promoting functions of histone Kcr and Kla during development.

scholarly journals Genome-wide proximity between RNA polymerase and DNA topoisomerase I supports transcription in Streptococcus pneumoniae

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009542
Author(s):  
María-José Ferrándiz ◽  
Pablo Hernández ◽  
Adela G. de la Campa
Keyword(s):  
Streptococcus Pneumoniae ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Sequence Motifs ◽  
Dna Topoisomerase ◽  
Genome Wide

Streptococcus pneumoniae is a major cause of disease and death that develops resistance to multiple antibiotics. DNA topoisomerase I (TopoI) is a novel pneumococcal drug target. TopoI is the sole type-I pneumococcal topoisomerase that regulates supercoiling homeostasis in this bacterium. In this study, a direct in vitro interaction between TopoI and RNA polymerase (RNAP) was detected by surface plasmon resonance. To understand the interplay between transcription and supercoiling regulation in vivo, genome-wide association of RNAP and TopoI was studied by ChIP-Seq. RNAP and TopoI were enriched at the promoters of 435 and 356 genes, respectively. Higher levels of expression were consistently measured in those genes whose promoters recruit both RNAP and TopoI, in contrast with those enriched in only one of them. Both enzymes occupied a narrow region close to the ATG codon. In addition, RNAP displayed a regular distribution throughout the coding regions. Likewise, the summits of peaks called with MACS tool, mapped around the ATG codon in both cases. However, RNAP showed a broader distribution towards ATG-downstream positions. Remarkably, inhibition of RNAP with rifampicin prevented the localization of TopoI at promoters and, vice versa, inhibition of TopoI with seconeolitsine prevented the binding of RNAP to promoters. This indicates a functional interplay between RNAP and TopoI. To determine the molecular factors responsible for RNAP and TopoI co-recruitment, we looked for DNA sequence motifs. We identified a motif corresponding to a -10-extended promoter for TopoI and for RNAP. Furthermore, RNAP was preferentially recruited to genes co-directionally oriented with replication, while TopoI was more abundant in head-on genes. TopoI was located in the intergenic regions of divergent genes pairs, near the promoter of the head-on gene of the pair. These results suggest a role for TopoI in the formation/stability of the RNAP-DNA complex at the promoter and during transcript elongation.

scholarly journals In Vivo Dissection of the Helicobacter pylori Fur Regulatory Circuit by Genome-Wide Location Analysis

2006 ◽  
Vol 188 (13) ◽  
pp. 4654-4662 ◽  
Author(s):  
Alberto Danielli ◽  
Davide Roncarati ◽  
Isabel Delany ◽  
Valentina Chiarini ◽  
Rino Rappuoli ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Pathogenic Bacteria ◽  
Iron Homeostasis ◽  
Location Analysis ◽  
Transcriptional Level ◽  
Regulatory Circuit ◽  
Genome Wide ◽  
A Genome ◽  
H Pylori

ABSTRACT Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. In Helicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type and fur deletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by the fur mutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes, hpn2 and flaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in the fur mutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level in H. pylori and points to regulatory functions extending beyond the classical Fur repression paradigm.

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