Regulation of Messenger Rna-Binding Proteins by Protein Kinases A and C

2002 ◽  
pp. 193-211
Author(s):  
Richard A. Jungmann
Keyword(s):  
Protein Kinases ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

Messenger-RNA-binding proteins and the messages they carry

2002 ◽  
Vol 3 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Gideon Dreyfuss ◽  
V. Narry Kim ◽  
Naoyuki Kataoka
Keyword(s):  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

scholarly journals Vectorial Channeling as a Mechanism for Translational Control by Functional Prions and Condensates

2021 ◽  
Author(s):  
Xinyu Gu ◽  
Nicholas P Schafer ◽  
Peter G Wolynes
Keyword(s):  
Experimental Data ◽  
Dendritic Spines ◽  
Translational Control ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Potential Of Mean Force ◽  
Translation Control ◽  
Through Diffusion

Translation of messenger RNA is regulated through a diverse set of RNA-binding proteins. A significant fraction of RNA-binding proteins contain prion-like domains which form functional prions. This raises the question of how prions can play a role in translational control. Local control of translation in dendritic spines by prions has been invoked in the mechanism of synaptic plasticity and memory. We show how channeling through diffusion and processive translation cooperate in highly ordered mRNA/prion aggregates as well as in less ordered mRNA/protein condensates depending on their substructure. We show the direction of translational control, whether it is repressive or activating, depends on the polarity of the mRNA distribution in mRNA/prion assemblies which determines whether vectorial channeling can enhance recycling of ribosomes. Our model also addresses the effect of changes of substrate concentration in assemblies that have been suggested previously to explain translation control by assemblies through the introduction of a potential of mean force biasing diffusion of ribosomes inside the assemblies. The results from the model are compared with the experimental data on translational control by two functional RNA-binding prions, CPEB involved in memory and Rim4 involved in gametogenesis.

scholarly journals Possible involvement of messenger RNA-associated proteins in protein synthesis.

1982 ◽  
Vol 93 (3) ◽  
pp. 893-898 ◽  
Author(s):  
H P Schmid ◽  
K Köhler ◽  
B Setyono
Keyword(s):  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Ascites Cell ◽  
Free System ◽  
Molecular Weights ◽  
Messenger Ribonucleoprotein ◽  
Associated Proteins ◽  
Globin Synthesis

Two distinct forms of globin messenger RNA were isolated from mouse spleen cells infected with Friend erythroleukemia virus: polyribosomal messenger ribonucleoprotein particles (15S mRNP), and their corresponding protein-free mRNAs obtained by chemical deproteinization. The translation efficiencies of both messenger forms were assayed in a Krebs II ascites cell-free system. Selective removal of RNA-binding proteins from the ascites cell lysate did not affect globin synthesis when the mRNA was supplied as 15S mRNP; deproteinized mRNA however was not translated. Only in the presence of two fractions of RNA-binding proteins was the protein-free mRNA translated. Some of the RNA-binding proteins have the same molecular weights and isoelectric points as the principal proteins of 15S mRNP.

scholarly journals HRPK-1, a conserved KH-domain protein, modulates microRNA activity during Caenorhabditis elegans development

2019 ◽  
Author(s):  
Li Li ◽  
Isana Veksler-Lublinsky ◽  
Anna Y. Zinovyeva
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genetic Interaction ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
C Elegans ◽  
Multiple Levels

AbstractmicroRNAs (miRNAs) are potent regulators of gene expression that function in diverse developmental and physiological processes. Argonaute proteins loaded with miRNAs form the miRNA Induced Silencing Complexes (miRISCs) that repress gene expression at the post-transcriptional level. miRISCs target genes through partial sequence complementarity between the miRNA and the target mRNA’s 3’ UTR. In addition to being targeted by miRNAs, these mRNAs are also extensively regulated by RNA-binding proteins (RBPs) through RNA processing, transport, stability, and translation regulation. While the degree to which RBPs and miRISCs functionally interact to regulate gene expression is likely extensive, we have only begun to unravel these functional interactions. An RNAi-based screen of putative ALG-1 Argonaute interactors has identified a role for a conserved RNA binding protein, HRPK-1, in modulating miRNA activity during C. elegans development. Here, we report the physical and genetic interaction between HRPK-1 and ALG-1/miRNAs. Specifically, we report the genetic and molecular characterizations of hrpk-1 and its role in C. elegans development and miRNA-mediated target repression. We show that loss of hrpk-1 causes numerous developmental defects and enhances the mutant phenotypes associated with reduction of miRNA activity, including those of lsy-6, mir-35-family, and let-7-family miRNAs. In addition to hrpk-1 genetic interaction with these miRNA families, hrpk-1 is required for efficient regulation of lsy-6 target cog-1. We report that hrpk-1 may play a role in miRNA processing but is not globally required for mature miRNA biogenesis or ALG-1/AIN-1 miRISC assembly and confirm HRPK-1 ability to co-precipitate with ALG-1. We suggest that HRPK-1 may functionally interact with miRNAs on multiple levels to enhance miRNA/miRISC gene regulatory activity and present several models for its activity.Author summarymicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. The core microRNA Induced Silencing Complex (miRISC), composed of Argonaute, mature microRNA, and GW182 protein effector, assembles on the target messenger RNA and inhibits translation or leads to messenger RNA degradation. RNA binding proteins interface with miRNA pathways on multiple levels to coordinate gene expression regulation. Here, we report identification and characterization of HRPK-1, a conserved RNA binding protein, as a physical and functional interactor of miRNAs. We confirm the physical interaction between HRPK-1, an hnRNPK homolog, and Argonaute ALG-1. We report characterizations of hrpk-1 role in development and its functional interactions with multiple miRNA families. We suggest that HRPK-1 promotes miRNA activity on multiple levels in part by contributing to miRNA processing and by coordinating with miRISC at the level of target RNAs. This work contributes to our understanding of how RNA binding proteins and auxiliary miRNA cofactors may interface with miRNA pathways to modulate miRNA gene regulatory activity.

scholarly journals High-Throughput Translational Profiling with riboPLATE-seq

2019 ◽  
Author(s):  
Jordan B. Metz ◽  
Nicholas J. Hornstein ◽  
Sohani Das Sharma ◽  
Jeremy Worley ◽  
Peter A. Sims
Keyword(s):  
Protein Synthesis ◽  
Protein Kinases ◽  
High Throughput ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Library Preparation ◽  
Translational Machinery ◽  
Technological Limitations ◽  
Ribosome Association

ABSTRACTProtein synthesis is dysregulated in many diseases, but we lack a systems-level picture of how signaling molecules and RNA binding proteins interact with the translational machinery, largely due to technological limitations. Here we present riboPLATE-seq, a scalable method for generating paired libraries of ribosome-associated and total mRNA. As an extension of the PLATE-seq protocol, riboPLATE-seq utilizes barcoded primers for pooled library preparation, but additionally leverages rRNA immunoprecipitation on whole polysomes to measure ribosome association (RA). We demonstrate the performance of riboPLATE-seq and its utility in detecting translational alterations induced by inhibition of protein kinases.

scholarly journals Inhibition of tristetraprolin deadenylation by poly(A) binding protein

2008 ◽  
Vol 295 (3) ◽  
pp. G421-G430 ◽  
Author(s):  
Robert M. Rowlett ◽  
Carol A. Chrestensen ◽  
Melanie J. Schroeder ◽  
Mary G. Harp ◽  
Jared W. Pelo ◽  
...  
Keyword(s):  
Map Kinase ◽  
Messenger Rna ◽  
Protein Production ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
P38 Map Kinase ◽  
Raw264.7 Macrophages ◽  
Necrosis Factor

Tristetraprolin (TTP) is the prototype for a family of RNA binding proteins that bind the tumor necrosis factor (TNF) messenger RNA AU-rich element (ARE), causing deadenylation of the TNF poly(A) tail, RNA decay, and silencing of TNF protein production. Using mass spectrometry sequencing we identified poly(A) binding proteins-1 and -4 (PABP1 and PABP4) in high abundance and good protein coverage from TTP immunoprecipitates. PABP1 significantly enhanced TNF ARE binding by RNA EMSA and prevented TTP-initiated deadenylation in an in vitro macrophage assay of TNF poly(A) stability. Neomycin inhibited TTP-promoted deadenylation at concentrations shown to inhibit the deadenylases poly(A) ribonuclease and CCR4. Stably transfected RAW264.7 macrophages overexpressing PABP1 do not oversecrete TNF; instead they upregulate TTP protein without increasing TNF protein production. The PABP1 inhibition of deadenylation initiated by TTP does not require the poly(A) binding regions in RRM1 and RRM2, suggesting a more complicated interaction than simple masking of the poly(A) tail from a 3′-exonuclease. Like TTP, PABP1 is a substrate for p38 MAP kinase. Finally, PABP1 stabilizes cotransfected TTP in 293T cells and prevents the decrease in TTP levels seen with p38 MAP kinase inhibition. These findings suggest several levels of functional antagonism between TTP and PABP1 that have implications for regulation of unstable mRNAs like TNF.

scholarly journals Convergent Evidence That ZNF804A Is a Regulator of Pre-messenger RNA Processing and Gene Expression

2018 ◽  
Vol 45 (6) ◽  
pp. 1267-1278 ◽  
Author(s):  
Ria M Chapman ◽  
Caroline L Tinsley ◽  
Matthew J Hill ◽  
Marc P Forrest ◽  
Katherine E Tansey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Autism Spectrum Disorder ◽  
Messenger Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Splicing Factors ◽  
Alternatively Spliced

Abstract Genome-wide association studies have linked common variation in ZNF804A with an increased risk of schizophrenia. However, little is known about the biology of ZNF804A and its role in schizophrenia. Here, we investigate the function of ZNF804A using a variety of complementary molecular techniques. We show that ZNF804A is a nuclear protein that interacts with neuronal RNA splicing factors and RNA-binding proteins including RBFOX1, which is also associated with schizophrenia, CELF3/4, components of the ubiquitin-proteasome system and the ZNF804A paralog, GPATCH8. GPATCH8 also interacts with splicing factors and is localized to nuclear speckles indicative of a role in pre-messenger RNA (mRNA) processing. Sequence analysis showed that GPATCH8 contains ultraconserved, alternatively spliced poison exons that are also regulated by RBFOX proteins. ZNF804A knockdown in SH-SY5Y cells resulted in robust changes in gene expression and pre-mRNA splicing converging on pathways associated with nervous system development, synaptic contact, and cell adhesion. We observed enrichment (P = 1.66 × 10–9) for differentially spliced genes in ZNF804A-depleted cells among genes that contain RBFOX-dependent alternatively spliced exons. Differentially spliced genes in ZNF804A-depleted cells were also enriched for genes harboring de novo loss of function mutations in autism spectrum disorder (P = 6.25 × 10–7, enrichment 2.16) and common variant alleles associated with schizophrenia (P = .014), bipolar disorder and schizophrenia (P = .003), and autism spectrum disorder (P = .005). These data suggest that ZNF804A and its paralogs may interact with neuronal-splicing factors and RNA-binding proteins to regulate the expression of a subset of synaptic and neurodevelopmental genes.

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