A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs “talk” to each other using microRNA response elements (MREs) as letters of a new language. We propose that this “competing endogenous RNA” (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Register an Account If you do not have an account, create one by clicking the button below, and take full advantage of this site's features.
An HNF4α-miRNA Inflammatory Feedback Circuit Regulates Hepatocellular Oncogenesis. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 HNF4α Suppression through miR-24 and miR-629 Induces Hepatocellular Transformation (A) Soft agar colony assay of nontransformed immortalized hepatocytes (IMH1, IMH2) treated for 48 hr with siRNA-negative control (siNC) or two different siRNAs against HNF4α (siHNF4α#1, siHNF4α#2). (B) Tumor volume (mean ± SD) in mice injected with IMH1 cells untreated or treated for 48 hr with siRNA NC, siHNF4α#1, or siHNF4α#2. (C) Effects of microRNAs (primary screen) on HNF4α luciferase activity in HepG2 cells (top). (D) HNF4α mRNA levels (mean ± SD of three independent experiments) assessed by real-time RT-PCR analysis in HepG2, Hep3B, and SNU-449 cells untreated or treated with 100 nM miR NC or miR-24 and/or miR-629 for 48 hr. (E) HNF4α protein levels in HepG2 cells untreated or treated with 100 nM miR NC or miR-24 and/or miR-629 for 48 hr.
Figure 2 Figure 3. Cancer Cell - Polycomb Regulates NF-κB Signaling in Cancer through miRNA. Dual Regulation of miRNA Biogenesis Generates Target Specificity in Neurotrophin-Induced Protein Synthesis. Figure S1 Composition of Neuronal P Bodies, Related to Figure 1 (A) Endogenous Dcp1a (top, red) colocalizes with GFP-Dcp1a (middle, green) in a confocal projection of hippocampal pyramidal neuron dendrites. (Bottom) Overlaid image. (B) mCherry-tagged Dcp1a (top, red) colocalizes with GFP-tagged Ago2 (middle, green) in a confocal projection. (Bottom) Overlaid image. (C) Endogenous Rck/p54 (top, red) colocalizes with endogenous GW182 (middle, green) in a confocal projection. (Bottom) Overlaid image. (D) Consistent with the lack of translation in P bodies, endogenous ribosomal RNA, stained with Y10b (top, red) does not colocalize with GFP-tagged Dcp1a (middle, green) in dendrites of hippocampal pyramidal neurons.
(E) mCherry-tagged Dcp1a (top, red) does not colocalize with GFP-tagged Staufen (middle, green) in confocal projections from dendrites of hippocampal pyramidal neurons. (F) EBFP2-tagged Dcp1a (BFP-Dcp1a; top, blue) colocalizes with YFP-tagged Pat1b (YFP-Pat1b; middle, green). Elsevier introduces Genome Viewer | Cell Press Daily News Aggregator.
3′ End Formation of PIWI-Interacting RNAs In Vitro. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 Siwi, but Not BmAgo3, Preferentially Incorporates 1U RNA In Vitro (A and B) 26 nt or 50 nt 5′-radiolabeled RNAs with 5′ U, A, G, or C were incubated in 17,000 × g lysate from BmN4 cells expressing FLAG-Siwi (A) or FLAG-BmAgo3 (B), and the associated RNAs were immunopurified by anti-FLAG antibody. Input samples were diluted >500 fold. Siwi showed a strong preference for 1U, whereas BmAgo3 did not. Figure 2 3′ End Trimming of piRNA In Vitro (A) The experimental scheme for (B). (B) Naked 1U-50 RNA was incubated with lysis buffer (mock), 17,000 × g lysate, crude lysate, 1000 × g lysate, and resuspended 1000 × g pellet.
(C) The experimental scheme for (D). Figure 3 Trimmer Is a Mg2+-Dependent 3′ to 5′ Exonuclease (A) Trimming activity in the presence of EDTA or EGTA. (D) Siwi-bound 1U-26–39 and 1U-50 RNAs were incubated with 1000 × g pellet. Figure 4. 3′ End Formation of PIWI-Interacting RNAs In Vitro. A Critical Role for Noncoding 5S rRNA in Regulating Mdmx Stability. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 5S rRNA Directly Interacts with Mdmx Both In Vitro and In Vivo (A) The Mdmx complex affinity-purified from the whole extract of the U2OS/FLAG-Mdmx-HA stable cell line (lanes 4 and 5) were incubated with RNase A (lane 4) or the buffer alone (lane 5) and analyzed by SDS-PAGE and silver staining. (B) Coimmunoprecipitation of 5S rRNA with Mdmx from U2OS cells. (C) Mdmx specifically interacts with 5S rRNA. (D) Mdmx directly interacts with 5S rRNA. [32P] UTP-labeled 5S rRNA was incubated with 75 ng of His-Mdm2 (lane 2) or 60 ng of His-Mdmx (lane 3) for 45 min at room temperature and analyzed by native gel electrophoresis and autoradiography.
(E) Mdmx, but not p53 or Mdm2, interacts with 5S rRNA. Figure 2 RNAi-Mediated Knockdown of 5S rRNA Does Not Affect the Formation of the Large Ribosomal RNA-Protein Complex, But Induces Mdmx Degradation Figure 3 Summary. A Date with Telomerase: Pick You Up at S Phase. A Pre-mRNA Degradation Pathway that Selectively Targets Intron-Containing Genes Requires the Nuclear Poly(A)-Binding Protein. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 Pab2 Regulates the Expression of rpl30-2 at the Level of the Pre-mRNA (A) Northern blot analysis of RNA from wild-type (lanes 1 and 3) and pab2Δ (lanes 2 and 4) strains.
The blot was hybridized using a DNA probe complementary to rpl30-2 exon 1 (lanes 1 and 2) and intron (lanes 3 and 4) sequences. The blot was also probed for rpl30-1 and srp7 transcripts. (B) Northern blot analysis of RNA from wild-type (lanes 1 and 4), pab2Δ (lanes 2 and 5), and rrp6Δ (lanes 3 and 6) strains that express rpl30-2 from intron-containing (lanes 1–3) and intronless (RPL30-2Δi; lanes 4–6) constructs. (C) Quantitative PCR analysis of rpl30-2 mRNA level in the same strains described in (B) using a primer pair in which one primer spans the exon-exon junction. See also Figure S1 . Figure 2 Pab2 and the Nuclear Exosome Control rpl30-2 Expression See also Figure S2 . Figure 3. A Primate Herpesvirus Uses the Integrator Complex to Generate Viral MicroRNAs. To view the full text, please login as a subscribed user or purchase a subscription.
Click here to view the full text on ScienceDirect. Figure 1 HVS miRNAs Are Located Directly Downstream of HSUR Genes (A) Genomic locations of HSURs, protein-coding genes, and miRNAs. (B) Predicted secondary structures of primary transcripts for HSURs and miRNAs. (C) RT-PCR identification of transcripts containing both HSURs and miRNAs in marmoset T cells latently infected with HVS. Figure 2 HVS miRNAs Are Part of Active RISC Complexes (A) Northern blot showing coimmunoprecipitation of HVS miRNAs or host-encoded miR-16 from extracts of virally transformed marmoset T cells with control (C) anti-HA (lane 3) or anti-Ago (αAgo, lane 5) antibody.
Figure 3 Mutational Analysis of cis Elements Required for Expression of HSUR4-Linked miRNAs The HSUR4 proximal sequence element (PSE) and the primary transcript containing HSUR4 and its linked miRNAs (highlighted in gray) are shown. Figure 4 Figure 5 Figure 6 Figure 7 Summary. A Specific Function for the Histone Chaperone NASP to Fine-Tune a Reservoir of Soluble H3-H4 in the Histone Supply Chain. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 NASP Maintains a Soluble Pool of Histones H3.1/H3.3-H4 (A) Experimental and cellular fractionation scheme for assessing the effect of NASP depletion on soluble and salt-extractable extracts. See Figure S1 A and the Experimental Procedures for full details. (B) siRNA-mediated depletion of NASP destabilizes the soluble—but not salt-extractable—pool of histones H3 and H4. (C) NASP depletion leads to a loss of soluble H3.1 and H3.3.
(D) Either e-tNASP or e-sNASP can maintain the soluble H3-H4 pool upon endogenous NASP depletion. Figure 2 NASP Overexpression Increases the Soluble H3-H4 Pool (Top) Experimental scheme. Figure 3 NASP Interacts with the N Terminus of H3 and Has a Unique Function to Maintain a Soluble Pool of H3-H4 (A) NASP is in complex with multiple partners in vivo. (D) NASP binds preferentially to an N-terminal domain of histone H3. Summary. A Universal RNA Polymerase II CTD Cycle Is Orchestrated by Complex Interplays between Kinase, Phosphatase, and Isomerase Enzymes along Genes. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 A Uniform CTD Cycle at Most Transcribed Genes (A) Profile of RNAPII using either anti-CTD (8WG16), anti-myc (9E10; Rpb1-9myc), or anti-Rpb3 (W0012) antibodies on a metagene made with long (1500–2500 bp) and transcribed genes (based on 8WG16 average binding across the open reading frame [ORF]).
(B) Profile of RNAPII (8WG16) and its phosphorylation marks (P-Ser2 [H5 and 3E10], P-Ser5 [H14 and 3E8], P-Ser7 [4E12]) along metagenes representing three classes of genes based on average gene length (see Experimental Procedures for details). Profiles are shown for long (2,000 +/− 500 bp; solid line), medium size (1,000 +/− 250 bp; dashed line) and small (500 +/− 100 bp; dotted line) genes.
(C–E) Genomic regions harboring genes that show canonical (Box1 and Box2) and noncanonical (Box3–Box5) CTD phosphoserine profiles. Figure 2 Figure 3 Figure 4 Figure 5 Summary. A Universal RNA Polymerase II CTD Cycle Is Orchestrated by Complex Interplays between Kinase, Phosphatase, and Isomerase Enzymes along Genes. Acetylation Regulates the Stability of a Bacterial Protein: Growth Stage-Dependent Modification of RNase R.
To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 Binding of Exponential Phase and Stationary Phase RNase R to tmRNA-SmpB Complex (A) Increasing amounts of purified RNase R were mixed with a constant amount of GST-SmpB and tmRNA for pull-down assays as described in Experimental Procedures . RNase R and GST-SmpB in the eluant from each pull-down were resolved on 8% SDS-PAGE and detected by purified RNase R antibody and anti-GST mAb, respectively. (B) Quantification of three independent experiments carried out as shown in (A). The amount of exponential phase RNase R pulled down was set at 100% for each amount of RNase R added, and the corresponding value for the stationary phase protein is shown.
(C) Binding of exponential (Exp) or stationary (Sta) phase RNase R to tmRNA-SmpB complex. Figure 2 Structural Analysis of Exponential Phase and Stationary Phase RNase R Figure 3 Figure 4 Highlights Summary. Alternative miRNA Biogenesis Pathways and the Interpretation of Core miRNA Pathway Mutants. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Since the establishment of a canonical animal microRNA biogenesis pathway driven by the RNase III enzymes Drosha and Dicer, an unexpected variety of alternative mechanisms that generate functional microRNAs have emerged. We review here the many Drosha-independent and Dicer-independent microRNA biogenesis strategies characterized over the past few years.
Beyond reflecting the flexibility of small RNA machineries, the existence of noncanonical pathways has consequences for interpreting mutants in the core microRNA machinery. Such mutants are commonly used to assess the consequences of “total” microRNA loss, and indeed, they exhibit many overall phenotypic similarities. Register an Account If you do not have an account, create one by clicking the button below, and take full advantage of this site's features. Alternative Ubiquitin Activation/Conjugation Cascades Interact with N-End Rule Ubiquitin Ligases to Control Degradation of RGS Proteins. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.
Figure 1 Identification of UBR1, UBR2, and UBR3 as Targets of the USE1 Ubiquitin conjugating Enzyme (A) Scheme depicting the yeast three-hybrid screening strategy employed to identify proteins interacting with USE1. (B) Domain structures of UBR1, UBR2, and UBR3, along with the positions of the cDNA clones identified in our yeast three-hybrid screen.
(C) Flow chart for proteomic analysis of 293T cells stably expressing HA-USE1. (D) Summary of proteomic data, depicting total spectral counts (TSCs), DN-scores, and Z-scores for proteins found in association with HA-USE1. Figure 2 USE1 Interacts with UBR Proteins via the RING Domain (A) Extracts from mouse NIH 3T3 cells were subjected to immunoprecipitation with either control IgG or α-USE1 antibodies, and the presence of UBR1 and UBR2 were determined by immunoblotting. Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Summary. An RNA Reset Button. Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation. Figure 5 Identification of tiRNA-Interacting Proteins (A) Validation of selected candidate 5′-tiRNAAla-binding proteins. Proteins bound to biotinylated control RNA and 5′-tiRNAAla were purified using streptavidine beads, subjected to the indicated salt washes (0.1 M, 0.3 M, and 0.5M), eluted, then analyzed by western blotting using corresponding antibodies.
For list of interacting proteins, see Table S3 . (B) tiRNA-binding proteins required for 5′-tiRNAAla-induced SG assembly. (C) YB-1 is part of a complex displaced by 5′-tiRNAAla from m7GTP-Sepharose. (D) YB-1 is required for 5′-tiRNA-induced translational repression. (E) YB-1 is required for stress- and ANG-induced translational repression. Another “Loophole” in miRNA Processing. Applied Force Provides Insight into Transcriptional Pausing and Its Modulation by Transcription Factor NusA. To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect. Figure 1 Single-Molecule Transcription Assay (A) Experimental geometry for the DNA-pulling dumbbell assay (not to scale).
(B) Engineered transcription templates carrying the his pause element, as previously described ( Herbert et al., 2006 ). (C) Six representative records of RNAP elongation on the his repetitive template in the presence of 0.5 μM NusA (blue) (N = 34) or absence of NusA (red) (N = 45) under 7.5 pN assisting load at 1 mM NTPs. Figure 2 Kinetic Schemes for Transcriptional Elongation and Pausing (A) Generalized kinetic scheme for elongation and pausing, with the main RNA synthesis pathway displayed along the top (green boxes).
Figure 3 Single-Molecule Force-Velocity Relationships Figure 4 Pausing Statistics as a Function of Force Figure 5 Sequence-Specific Pauses Are Influenced by NusA and Load Figure 6 Figure 7 Highlights Summary Register an Account. Ars2 Promotes Proper Replication-Dependent Histone mRNA 3′ End Formation. Figure 1 Ars2 Regulates a Subset of microRNAs (A) HeLa cells were transfected with control siRNA or three siRNAs targeted to either Ars2 (Ars2-1, Ars2-2, Ars2-3) or DGCR8 (DGCR8-1, DGCR8-2, DGCR8-3). Protein was harvested 3 days following transfection to confirm specific depletion of Ars2 or DGCR8 by western blot. (B) HeLa cells were transfected with the siRNAs as in (A) and RNA was isolated 3 days later and analyzed separately on Affymetrix GeneChip® miRNA Arrays.
The number of miRNAs that decreased at least 2-fold (log2) following transfection of all three siRNAs per gene is depicted by Venn diagram. (C) Bar graphs showing 27 miRNAs determined by microarray to decrease 2-fold (log2) or more following depletion of DGCR8 or Ars2. (D) Bar graphs showing 6 miRNAs determined by microarray to decrease 2-fold (log2) or more following depletion of Ars2 but not DGCR8. (E) HeLa cells were transfected with two siRNAs targeted to Ars2 (Ars2-1, Ars2-2) or a control siRNA (ctl).
Figure 2 Figure 3. Autoantigen La Promotes Efficient RNAi, Antiviral Response, and Transposon Silencing by Facilitating Multiple-Turnover RISC Catalysis. Cell Adhesion-Dependent Control of MicroRNA Decay. Competing for the Clamp: Promoting RNA Polymerase Processivity and Managing the Transition from Initiation to Elongation. Conservation between the RNA Polymerase I, II, and III Transcription Initiation Machineries. Cross-Regulation between an Alternative Splicing Activator and a Transcription Repressor Controls Neurogenesis. Decapping of Long Noncoding RNAs Regulates Inducible Genes. Decapping of Long Noncoding RNAs Regulates Inducible Genes. Deciphering 3′ss Selection in the Yeast Genome Reveals an RNA Thermosensor that Mediates Alternative Splicing.
Deciphering 3′ss Selection in the Yeast Genome Reveals an RNA Thermosensor that Mediates Alternative Splicing. Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1. Dual Function of Sdh3 in the Respiratory Chain and TIM22 Protein Translocase of the Mitochondrial Inner Membrane. Dynamic Protein-Protein Interaction Wiring of the Human Spliceosome. Engineering Biological Systems with Synthetic RNA Molecules. Essential Features and Rational Design of CRISPR RNAs that Function with the Cas RAMP Module Complex to Cleave RNAs.
Essential Features and Rational Design of CRISPR RNAs that Function with the Cas RAMP Module Complex to Cleave RNAs. Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes. Functional Expansion of the tRNA World under Stress. Genomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin Interactions. Get Back TFIIF, Don't Let Me Gdown1. Gimme Phospho-Serine Five! Capping Enzyme Guanylyltransferase Recognition of the RNA Polymerase II CTD. GW182 Proteins Directly Recruit Cytoplasmic Deadenylase Complexes to miRNA Targets. Heterotypic piRNA Ping-Pong Requires Qin, a Protein with Both E3 Ligase and Tudor Domains. Heterotypic piRNA Ping-Pong Requires Qin, a Protein with Both E3 Ligase and Tudor Domains. Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA. Immobilization of Proteins in the Nucleolus by Ribosomal Intergenic Spacer Noncoding RNA.
Integrative Regulatory Mapping Indicates that the RNA-Binding Protein HuR Couples Pre-mRNA Processing and mRNA Stability. Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex. Intragenic Enhancers Act as Alternative Promoters. In Vivo and Transcriptome-wide Identification of RNA Binding Protein Target Sites. Live Cell Imaging of Telomerase RNA Dynamics Reveals Cell Cycle-Dependent Clustering of Telomerase at Elongating Telomeres. MCPIP1 Ribonuclease Antagonizes Dicer and Terminates MicroRNA Biogenesis through Precursor MicroRNA Degradation.
Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit. MicroRNA Destabilization Enables Dynamic Regulation of the miR-16 Family in Response to Cell-Cycle Changes. Molecular Mechanisms of Long Noncoding RNAs. Policing Cells under Stress: Noncoding RNAs Capture Proteins in Nucleolar Detention Centers. Policing Cells under Stress: Noncoding RNAs Capture Proteins in Nucleolar Detention Centers.
Polycomb Protein Ezh1 Promotes RNA Polymerase II Elongation. R We There Yet? R-Loop Hazards to Finishing the Journey. RAM/Fam103a1 Is Required for mRNA Cap Methylation. Reconsidering Movement of Eukaryotic mRNAs between Polysomes and P Bodies. Regional Specialization: The NEXT Big Thing in Nuclear RNA Turnover. Regulation by Small RNAs in Bacteria: Expanding Frontiers. Regulatory RNA: The New Age. RNA Homeostasis Governed by Cell Type-Specific and Branched Feedback Loops Acting on NMD. RNA Homeostasis Governed by Cell Type-Specific and Branched Feedback Loops Acting on NMD.
RNA-Binding Protein HuD Controls Insulin Translation. RNase H and Multiple RNA Biogenesis Factors Cooperate to Prevent RNA:DNA Hybrids from Generating Genome Instability. RNase H and Postreplication Repair Protect Cells from Ribonucleotides Incorporated in DNA. rRNA Pseudouridylation Defects Affect Ribosomal Ligand Binding and Translational Fidelity from Yeast to Human Cells. SAGA and ATAC Histone Acetyl Transferase Complexes Regulate Distinct Sets of Genes and ATAC Defines a Class of p300-Independent Enhancers.
Scd6 Targets eIF4G to Repress Translation: RGG Motif Proteins as a Class of eIF4G-Binding Proteins. Ser7 Phosphorylation of the CTD Recruits the RPAP2 Ser5 Phosphatase to snRNA Genes. Single-Cell Analysis Reveals that Noncoding RNAs Contribute to Clonal Heterogeneity by Modulating Transcription Factor Recruitment. Structure and Mechanism of the CMR Complex for CRISPR-Mediated Antiviral Immunity. Sub1 and RPA Associate with RNA Polymerase II at Different Stages of Transcription. SUMO-Specific Protease 1 Is Critical for Early Lymphoid Development through Regulation of STAT5 Activation. The cAMP-Dependent Protein Kinase Signaling Pathway Is a Key Regulator of P Body Foci Formation.
The DEAD-Box Protein Ded1 Modulates Translation by the Formation and Resolution of an eIF4F-mRNA Complex. The Ewing Sarcoma Protein Regulates DNA Damage-Induced Alternative Splicing. The Initiation Factor TFE and the Elongation Factor Spt4/5 Compete for the RNAP Clamp during Transcription Initiation and Elongation. The Little Elongation Complex Regulates Small Nuclear RNA Transcription. The Mediator Couples Transcription and Splicing. The Noncoding RNA Mistral Activates Hoxa6 and Hoxa7 Expression and Stem Cell Differentiation by Recruiting MLL1 to Chromatin. The Polycomb Group Mutant esc Leads to Augmented Levels of Paused Pol II in the Drosophila Embryo.
The Structural Basis for Substrate Recognition by Mammalian Polynucleotide Kinase 3′ Phosphatase. The β Subunit Gate Loop Is Required for RNA Polymerase Modification by RfaH and NusG. Transcriptional Regulation by Pol II(G) Involving Mediator and Competitive Interactions of Gdown1 and TFIIF with Pol II. Transcriptome-wide Analysis of Regulatory Interactions of the RNA-Binding Protein HuR.
UneCLIPsing HuR Nuclear Function. Mutation of a U2 snRNA Gene Causes Global Disruption of Alternative Splicing and Neurodegeneration. Mutation of a U2 snRNA Gene Causes Global Disruption of Alternative Splicing and Neurodegeneration. Mutually Exclusive Binding of Telomerase RNA and DNA by Ku Alters Telomerase Recruitment Model. Reports - faq. RNA Dynamics in Aging Bacterial Spores. Single-Molecule Imaging of Transcriptionally Coupled and Uncoupled Splicing.
Structural Basis for Promoter −10 Element Recognition by the Bacterial RNA Polymerase σ Subunit. Structural Insights into RNA Recognition by RIG-I. The Human Mitochondrial Transcriptome.