scholarly journals AU-Rich Element RNA Binding Proteins: At the Crossroads of Post-Transcriptional Regulation and Genome Integrity

2021 ◽  
Vol 23 (1) ◽  
pp. 96
Author(s):  
Ahmed Sidali ◽  
Varsha Teotia ◽  
Nadeen Shaikh Solaiman ◽  
Nahida Bashir ◽  
Radhakrishnan Kanagaraj ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Cellular Survival ◽  
Novel Therapeutic Strategies ◽  
Post Transcriptional Regulation

Genome integrity must be tightly preserved to ensure cellular survival and to deter the genesis of disease. Endogenous and exogenous stressors that impose threats to genomic stability through DNA damage are counteracted by a tightly regulated DNA damage response (DDR). RNA binding proteins (RBPs) are emerging as regulators and mediators of diverse biological processes. Specifically, RBPs that bind to adenine uridine (AU)-rich elements (AREs) in the 3′ untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DDR and preserving genome integrity. Here we review eight established AU-RBPs (AUF1, HuR, KHSRP, TIA-1, TIAR, ZFP36, ZFP36L1, ZFP36L2) and their ability to maintain genome integrity through various interactions. We have reviewed canonical roles of AU-RBPs in regulating the fate of mRNA transcripts encoding DDR genes at multiple post-transcriptional levels. We have also attempted to shed light on non-canonical roles of AU-RBPs exploring their post-translational modifications (PTMs) and sub-cellular localization in response to genotoxic stresses by various factors involved in DDR and genome maintenance. Dysfunctional AU-RBPs have been increasingly found to be associated with many human cancers. Further understanding of the roles of AU-RBPS in maintaining genomic integrity may uncover novel therapeutic strategies for cancer.

scholarly journals RNA Binding Proteins and Genome Integrity

2017 ◽  
Vol 18 (7) ◽  
pp. 1341 ◽  
Author(s):  
Kensei Nishida ◽  
Yuki Kuwano ◽  
Tatsuya Nishikawa ◽  
Kiyoshi Masuda ◽  
Kazuhito Rokutan
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genome Integrity

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control

2019 ◽  
Vol 97 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Laura P.M.H. de Rooij ◽  
Derek C.H. Chan ◽  
Ava Keyvani Chahi ◽  
Kristin J. Hope
Keyword(s):  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cell Fate ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Control Of Gene Expression ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Post Transcriptional Regulation

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

scholarly journals Npl3, a new link between RNA-binding proteins and the maintenance of genome integrity

Cell Cycle ◽  
2014 ◽  
Vol 13 (10) ◽  
pp. 1524-1529 ◽  
Author(s):  
José M Santos-Pereira ◽  
Ana B Herrero ◽  
Sergio Moreno ◽  
Andrés Aguilera
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genome Integrity

scholarly journals Involvement of ELAV RNA-binding proteins in the post-transcriptional regulation of HO-1

2015 ◽  
Vol 8 ◽  
Author(s):  
Marialaura Amadio ◽  
Giovanni Scapagnini ◽  
Sergio Davinelli ◽  
Vittorio Calabrese ◽  
Stefano Govoni ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Post Transcriptional Regulation

scholarly journals Proteomic Analysis of the Kaposi's Sarcoma-Associated Herpesvirus Terminal Repeat Element Binding Proteins

2006 ◽  
Vol 80 (18) ◽  
pp. 9017-9030 ◽  
Author(s):  
Huaxin Si ◽  
Subhash C. Verma ◽  
Erle S. Robertson
Keyword(s):  
Proteomic Analysis ◽  
Kaposi's Sarcoma ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Kaposi’S Sarcoma ◽  
Terminal Repeat ◽  
Genome Maintenance ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Terminal repeat (TR) elements of Kaposi's sarcoma-associated herpesvirus (KSHV), the potential origin sites of KSHV replication, have been demonstrated to play important roles in viral replication and transcription and are most likely also critical for the segregation of the KSHV genome to daughter cells. To search for the cellular proteins potentially involved in KSHV genome maintenance, we performed affinity chromatography analysis, using KSHV TR DNA as the affinity ligand. Proteomic analysis was then carried out to identify the TR-interacting proteins. We identified a total of 123 proteins from both KSHV-positive and -negative cells, among which most were identified exclusively from KSHV-positive cells. These proteins were categorized as proliferation/cell cycle regulatory proteins, proteins involved in spliceosome components, such as heterogeneous nuclear ribonuclear proteins, the DEAD/H family, the switch/sucrose nonfermenting protein family, splicing factors, RNA binding proteins, transcription regulation proteins, replication factors, modifying enzymes, and a number of proteins that could not be broadly categorized. To support the proteomic results, the presence of four candidate proteins, ATR, BRG1, NPM1 and PARP-1, in the elutions was further characterized in this study. The binding and colocalization of these proteins with the TR were verified using chromatin immunoprecipitation and immunofluorescence in situ hybridization analysis. These newly identified TR binding proteins provide a number of clues and potential links to understanding the mechanisms regulating the replication, transcription, and genome maintenance of KSHV. This study will facilitate the generation and testing of new hypotheses to further our understanding of the mechanisms involved in KSHV persistence and its associated pathogenesis.

scholarly journals RNA-binding proteins involved in post-transcriptional regulation in bacteria

2015 ◽  
Vol 6 ◽  
Author(s):  
Elke Van Assche ◽  
Sandra Van Puyvelde ◽  
Jos Vanderleyden ◽  
Hans P. Steenackers
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Post Transcriptional Regulation

scholarly journals Trypanosoma brucei RNA Binding Proteins p34 and p37 Mediate NOPP44/46 Cellular Localization via the Exportin 1 Nuclear Export Pathway

2007 ◽  
Vol 6 (12) ◽  
pp. 2206-2213 ◽  
Author(s):  
Kristina Hellman ◽  
Kimberly Prohaska ◽  
Noreen Williams
Keyword(s):  
Amino Acid ◽  
Trypanosoma Brucei ◽  
Nuclear Export ◽  
Cellular Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Export Signal ◽  
Amino Acid Sequences ◽  
Protein Levels

ABSTRACT We have previously identified and characterized two novel nuclear RNA binding proteins, p34 and p37, which have been shown to interact with a family of nucleolar phosphoproteins, NOPP44/46, in Trypanosoma brucei. These proteins are nearly identical, the major difference being an 18-amino-acid insert in the N terminus of p37. In order to characterize the interaction between p34 and p37 and NOPP44/46, we have utilized an RNA interference (RNAi) cell line that specifically targets p34 and p37. Within these RNAi cells, we detected a disruption of a higher-molecular-weight complex containing NOPP44/46, as well as a dramatic increase in nuclear NOPP44/46 protein levels. We demonstrated that no change occurred in NOPP44/46 mRNA steady-state levels or stability, nor was there a change in cellular protein levels. These results led us to investigate whether p34 and p37 regulate NOPP44/46 cellular localization. Examination of the p34 and p37 amino acid sequences revealed a leucine-rich nuclear export signal, which interacts with the nuclear export factor exportin 1. Immune capture experiments demonstrated that p34, p37, and NOPP44/46 associate with exportin 1. When these experiments were performed with p34/p37 RNAi cells, NOPP44/46 no longer associated with exportin 1. Sequential immune capture experiments demonstrated that p34, p37, NOPP44/46, and exportin 1 exist in a common complex. Inhibiting exportin 1-mediated nuclear export led to an increase in nuclear NOPP44/46 proteins, indicating that they are exported from the nucleus via this pathway. Together, our results demonstrate that p34 and p37 regulate NOPP44/46 cellular localization by facilitating their association with exportin 1.

scholarly journals SPACE exploration of chromatin proteome to reveal associated RNA-binding proteins

2020 ◽  
Author(s):  
Mahmoud-Reza Rafiee ◽  
Julian A Zagalak ◽  
Giulia Tyzack ◽  
Rickie Patani ◽  
Jernej Ule ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genome Maintenance ◽  
Purification Method ◽  
Comprehensive Knowledge ◽  
Associated Proteins ◽  
Versatile Technique ◽  
Dna Binders ◽  
Lateral Sclerosis

AbstractChromatin is composed of many proteins that mediate intermolecular transactions with the genome. Comprehensive knowledge of these components and their interactions is necessary for insights into gene regulation and other activities; however, reliable identification of chromatin-associated proteins remains technically challenging. Here, we present SPACE (Silica Particle Assisted Chromatin Enrichment), a stringent and straightforward chromatin-purification method that helps identify direct DNA-binders separately from chromatin-associated proteins. We demonstrate SPACE’s unique strengths in three experimental set-ups: the sensitivity to detect novel chromatin-associated proteins, the quantitative nature to measure dynamic protein use across distinct cellular conditions, and the ability to handle 10-25 times less starting material than competing methods. In doing so, we reveal an unforeseen scale of association between over 500 nuclear RNA-binding proteins (RBPs) with chromatin and DNA, providing new insights into their roles as important regulators of genome maintenance and chromatin composition. Applied to iPSC-derived neural precursors, we discover a new role for the amyotrophic lateral sclerosis (ALS)-causing Valosin Containing Protein (VCP) in recruiting DNA-damage components to chromatin, thus paving the way for molecular mechanistic insights into the disease. SPACE is a fast and versatile technique with many applications.

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