scholarly journals ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

2020 ◽  
Vol 48 (19) ◽  
pp. 11097-11112
Author(s):  
S Chul Kwon ◽  
Harim Jang ◽  
Siyuan Shen ◽  
S Chan Baek ◽  
Kijun Kim ◽  
...  
Keyword(s):  
Mirna Biogenesis ◽  
Rnase Iii ◽  
Primary Transcript ◽  
High Affinity ◽  
Hydrophobic Groove ◽  
Dsrna Binding ◽  
N Terminus ◽  
Mirna Clusters ◽  
Mirna Biogenesis Pathway

Abstract The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate ‘cluster assistance’ in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.

scholarly journals ERH as a component of the Microprocessor facilitates the maturation of suboptimal microRNAs

2020 ◽  
Author(s):  
S. Chul Kwon ◽  
Harim Jang ◽  
Jihye Yang ◽  
Jeesoo Kim ◽  
S. Chan Baek ◽  
...  
Keyword(s):  
Rnase Iii ◽  
Primary Transcript ◽  
High Affinity ◽  
Dsrna Binding ◽  
N Terminus ◽  
Microprocessor Complex ◽  
Mirna Clusters ◽  
Enhancer Of Rudimentary ◽  
Mirna Pathway

ABSTRACTThe Microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here we identify Enhancer of Rudimentary Homolog (ERH) as a new component of the Microprocessor. ERH binds to a conserved region in the N-terminus of DGCR8. Knockdown of ERH or deletion of the DGCR8 N-terminus results in a decrease of processing of primary miRNAs with suboptimal hairpin structures that reside in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate “cluster assistance” in which the Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA pathway.

scholarly journals Regulation of signalling by microRNAs

2012 ◽  
Vol 40 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Roi Avraham ◽  
Yosef Yarden
Keyword(s):  
Transcriptional Repression ◽  
Signal Propagation ◽  
Cellular Responses ◽  
Mirna Biogenesis ◽  
Extracellular Signals ◽  
Genetic Switches ◽  
Control Stability ◽  
External Stimuli ◽  
Mirna Biogenesis Pathway

Stringent regulation of biochemical signalling pathways involves feedback and feedforward loops, which underlie robust cellular responses to external stimuli. Regulation occurs in all horizontal layers of signalling networks, primarily by proteins that mediate internalization of receptor–ligand complexes, dephosphorylation of kinases and their substrates, as well as transcriptional repression. Recent studies have unveiled the role of miRNAs (microRNAs), post-transcriptional regulators that control mRNA stability, as key modulators of signal propagation. By acting as genetic switches or fine-tuners, miRNAs can directly and multiply regulate cellular outcomes in response to diverse extracellular signals. Conversely, signalling networks temporally control stability, biogenesis and abundance of miRNAs, by regulating layers of the miRNA biogenesis pathway. In the present mini-review, we use a set of examples to illustrate the extensive interdependence between miRNAs and signalling networks.

scholarly journals Coupled RNA Processing and Transcription of Intergenic Primary MicroRNAs

2009 ◽  
Vol 29 (20) ◽  
pp. 5632-5638 ◽  
Author(s):  
Monica Ballarino ◽  
Francesca Pagano ◽  
Erika Girardi ◽  
Mariangela Morlando ◽  
Davide Cacchiarelli ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Rna Processing ◽  
Mirna Biogenesis ◽  
Rnase Iii ◽  
Primary Transcript ◽  
Attenuation Effect ◽  
Pol Ii ◽  
Chromatin Template ◽  
Precursor Mirnas ◽  
Efficient Expression

ABSTRACT The first step in microRNA (miRNA) biogenesis occurs in the nucleus and is mediated by the Microprocessor complex containing the RNase III-like enzyme Drosha and its cofactor DGCR8. Here we show that the 5′→3′ exonuclease Xrn2 associates with independently transcribed miRNAs and, in combination with Drosha processing, attenuates transcription in downstream regions. We suggest that, after Drosha cleavage, a torpedo-like mechanism acts on nascent long precursor miRNAs, whereby Xrn2 exonuclease degrades the RNA polymerase II-associated transcripts inducing its release from the template. While involved in primary transcript termination, this attenuation effect does not restrict clustered miRNA expression, which, in the majority of cases, is separated by short spacers. We also show that transcripts originating from a miRNA promoter are retained on the chromatin template and are more efficiently processed than those produced from mRNA or snRNA Pol II-dependent promoters. These data imply that coupling between transcription and processing promotes efficient expression of independently transcribed miRNAs.

scholarly journals Modulation of MicroRNA Processing by Dicer via Its Associated dsRNA Binding Proteins

2021 ◽  
Vol 7 (3) ◽  
pp. 57
Author(s):  
Toyotaka Yoshida ◽  
Yoshimasa Asano ◽  
Kumiko Ui-Tei
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mirna Biogenesis ◽  
Dependent Manner ◽  
Rnase Iii ◽  
Loop Region ◽  
Dsrna Binding ◽  
Essential Components ◽  
Microrna Processing

MicroRNAs (miRNAs) are small non-coding RNAs that are about 22 nucleotides in length. They regulate gene expression post-transcriptionally by guiding the effector protein Argonaute to its target mRNA in a sequence-dependent manner, causing the translational repression and destabilization of the target mRNAs. Both Drosha and Dicer, members of the RNase III family proteins, are essential components in the canonical miRNA biogenesis pathway. miRNA is transcribed into primary-miRNA (pri-miRNA) from genomic DNA. Drosha then cleaves the flanking regions of pri-miRNA into precursor-miRNA (pre-miRNA), while Dicer cleaves the loop region of the pre-miRNA to form a miRNA duplex. Although the role of Drosha and Dicer in miRNA maturation is well known, the modulation processes that are important for regulating the downstream gene network are not fully understood. In this review, we summarized and discussed current reports on miRNA biogenesis caused by Drosha and Dicer. We also discussed the modulation mechanisms regulated by double-stranded RNA binding proteins (dsRBPs) and the function and substrate specificity of dsRBPs, including the TAR RNA binding protein (TRBP) and the adenosine deaminase acting on RNA (ADAR).

scholarly journals PS2 - 197 DICER Governs Characteristics of Glioma Stem Cells and the Resulting Tumors in Xenograft Mouse Models of GBM

2016 ◽  
Vol 43 (S4) ◽  
pp. S15-S15
Author(s):  
S. Mansouri ◽  
S. Singh ◽  
A. Alamsahebpour ◽  
K. Burrell ◽  
M. Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Radiation Treatment ◽  
Proliferation Index ◽  
Mirna Biogenesis ◽  
Glioma Stem Cells ◽  
Novel Therapies ◽  
Rnase Iii ◽  
Lineage Differentiation ◽  
Tumorigenic Potential

The RNAse III endonuclease DICER is a key regulator of microRNA (miRNA) biogenesis and is frequently down-regulated in a variety of malignancies. We characterized the role of Dicer in glioblastoma (GB), specifically demonstrating its effects on the ability of glioma stem-like cells to form tumors in a mouse model of GB. DICER silencing in glioma stem-like cells (GSCs) reduced their stem cell characteristics, while tumors arising from these cells were more aggressive, larger in volume, and displayed a higher proliferation index and lineage differentiation. The resulting tumors, however, were more sensitive to radiation treatment. Our results demonstrate that DICER affects the tumorigenic potential of GSCs, providing a platform for analysis of specific relevant miRNAs and development of potentially novel therapies against GB.

The Role of the Initiator System in the Synthesis of Acidic Multifunctional Nanoparticles Designed for Molecular Imprinting of Proteins

2020 ◽  
Vol 65 (1) ◽  
pp. 28-41
Author(s):  
Marwa Aly Ahmed ◽  
Júlia Erdőssy ◽  
Viola Horváth
Keyword(s):  
Acrylic Acid ◽  
Binding Affinity ◽  
Molecular Imprinting ◽  
Low Temperatures ◽  
Ammonium Persulfate ◽  
Sodium Bisulfite ◽  
Multifunctional Nanoparticles ◽  
High Affinity ◽  
Initiator System

Multifunctional nanoparticles have been shown earlier to bind certain proteins with high affinity and the binding affinity could be enhanced by molecular imprinting of the target protein. In this work different initiator systems were used and compared during the synthesis of poly (N-isopropylacrylamide-co-acrylic acid-co-N-tert-butylacrylamide) nanoparticles with respect to their future applicability in molecular imprinting of lysozyme. The decomposition of ammonium persulfate initiator was initiated either thermally at 60 °C or by using redox activators, namely tetramethylethylenediamine or sodium bisulfite at low temperatures. Morphology differences in the resulting nanoparticles have been revealed using scanning electron microscopy and dynamic light scattering. During polymerization the conversion of each monomer was followed in time. Striking differences were demonstrated in the incorporation rate of acrylic acid between the tetramethylethylenediamine catalyzed initiation and the other systems. This led to a completely different nanoparticle microstructure the consequence of which was the distinctly lower lysozyme binding affinity. On the contrary, the use of sodium bisulfite activation resulted in similar nanoparticle structural homogeneity and protein binding affinity as the thermal initiation.

The role of SERT N-terminus in amphetamine-induced efflux

2016 ◽  
Vol 4 (Suppl. 3) ◽  
pp. A4.17
Author(s):  
Fatma Aslı Erdem
Keyword(s):  
N Terminus

Acid-Sensing Ion Channels

2020 ◽  
Author(s):  
Stefan Gründer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Excitatory Synapses ◽  
Detailed Characterization ◽  
High Affinity ◽  
Acid Sensing Ion Channels ◽  
Long Time ◽  
Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

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