scholarly journals Versatility of RNA-Binding Proteins in Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Laurence Wurth
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tumor Development ◽  
Posttranscriptional Control ◽  
Master Regulators ◽  
Binding Domains ◽  
Mrna Targets ◽  
Posttranscriptional Gene Regulation ◽  
A Cell

Posttranscriptional gene regulation is a rapid and efficient process to adjust the proteome of a cell to a changing environment. RNA-binding proteins (RBPs) are the master regulators of mRNA processing and translation and are often aberrantly expressed in cancer. In addition to well-studied transcription factors, RBPs are emerging as fundamental players in tumor development. RBPs and their mRNA targets form a complex network that plays a crucial role in tumorigenesis. This paper describes mechanisms by which RBPs influence the expression of well-known oncogenes, focusing on precise examples that illustrate the versatility of RBPs in posttranscriptional control of cancer development. RBPs appeared very early in evolution, and new RNA-binding domains and combinations of them were generated in more complex organisms. The identification of RBPs, their mRNA targets, and their mechanism of action have provided novel potential targets for cancer therapy.

scholarly journals Functional Roles of RNA-Binding Proteins in Plant Signaling

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 288
Author(s):  
Victor Muleya ◽  
Claudius Marondedze
Keyword(s):  
Stress Responses ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Structural Similarity ◽  
Plant Signaling ◽  
Affinity Capture ◽  
Functional Roles ◽  
Binding Domains ◽  
Mrna Targets

RNA-binding proteins (RBPs) are typical proteins that bind RNA through single or multiple RNA-binding domains (RBDs). These proteins have a functional role in determining the fate or function of the bound RNAs. A few hundred RBPs were known through in silico prediction based on computational assignment informed by structural similarity and the presence of classical RBDs. However, RBPs lacking such conventional RBDs were omitted. Owing to the recent mRNA interactome capture technology based on UV-crosslinking and fixing proteins to their mRNA targets followed by affinity capture purification and identification of RBPs by tandem mass spectrometry, several hundreds of RBPs have recently been discovered. These proteome-wide studies have colossally increased the number of proteins implicated in RNA binding and unearthed hundreds of novel RBPs lacking classical RBDs, such as proteins involved in intermediary metabolism. These discoveries provide wide insights into the post-transcriptional gene regulation players and their role in plant signaling, such as environmental stress conditions. In this review, novel discoveries of RBPs are explored, particularly on the evolving knowledge of their role in stress responses. The molecular functions of these RBPs, particularly focusing on those that do not have classical RBDs, are also elucidated at the systems level.

scholarly journals Identification of mRNAs Associated with αCP2-Containing RNP Complexes

2003 ◽  
Vol 23 (19) ◽  
pp. 7055-7067 ◽  
Author(s):  
Shelly A. Waggoner ◽  
Stephen A. Liebhaber
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Cell Function ◽  
Rna Binding Proteins ◽  
Translation Control ◽  
Viral Mrnas ◽  
Posttranscriptional Gene Regulation ◽  
Direct Binding

ABSTRACT Posttranscriptional controls in higher eukaryotes are central to cell differentiation and developmental programs. These controls reflect sequence-specific interactions of mRNAs with one or more RNA binding proteins. The α-globin poly(C) binding proteins (αCPs) comprise a highly abundant subset of K homology (KH) domain RNA binding proteins and have a characteristic preference for binding single-stranded C-rich motifs. αCPs have been implicated in translation control and stabilization of multiple cellular and viral mRNAs. To explore the full contribution of αCPs to cell function, we have identified a set of mRNAs that associate in vivo with the major αCP2 isoforms. One hundred sixty mRNA species were consistently identified in three independent analyses of αCP2-RNP complexes immunopurified from a human hematopoietic cell line (K562). These mRNAs could be grouped into subsets encoding cytoskeletal components, transcription factors, proto-oncogenes, and cell signaling factors. Two mRNAs were linked to ceroid lipofuscinosis, indicating a potential role for αCP2 in this infantile neurodegenerative disease. Surprisingly, αCP2 mRNA itself was represented in αCP2-RNP complexes, suggesting autoregulatory control of αCP2 expression. In vitro analyses of representative target mRNAs confirmed direct binding of αCP2 within their 3′ untranslated regions. These data expand the list of mRNAs that associate with αCP2 in vivo and establish a foundation for modeling its role in coordinating pathways of posttranscriptional gene regulation.

scholarly journals The Role of RNA-Binding Proteins in Vertebrate Neural Crest and Craniofacial Development

2021 ◽  
Vol 9 (3) ◽  
pp. 34
Author(s):  
Thomas E. Forman ◽  
Brenna J. C. Dennison ◽  
Katherine A. Fantauzzo
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Craniofacial Development ◽  
Specific Sequence ◽  
Altered Expression ◽  
Binding Domains

Cranial neural crest (NC) cells delaminate from the neural folds in the forebrain to the hindbrain during mammalian embryogenesis and migrate into the frontonasal prominence and pharyngeal arches. These cells generate the bone and cartilage of the frontonasal skeleton, among other diverse derivatives. RNA-binding proteins (RBPs) have emerged as critical regulators of NC and craniofacial development in mammals. Conventional RBPs bind to specific sequence and/or structural motifs in a target RNA via one or more RNA-binding domains to regulate multiple aspects of RNA metabolism and ultimately affect gene expression. In this review, we discuss the roles of RBPs other than core spliceosome components during human and mouse NC and craniofacial development. Where applicable, we review data on these same RBPs from additional vertebrate species, including chicken, Xenopus and zebrafish models. Knockdown or ablation of several RBPs discussed here results in altered expression of transcripts encoding components of developmental signaling pathways, as well as reduced cell proliferation and/or increased cell death, indicating that these are common mechanisms contributing to the observed phenotypes. The study of these proteins offers a relatively untapped opportunity to provide significant insight into the mechanisms underlying gene expression regulation during craniofacial morphogenesis.

PUB1: a major yeast poly(A)+ RNA-binding protein

1993 ◽  
Vol 13 (10) ◽  
pp. 6114-6123
Author(s):  
M J Matunis ◽  
E L Matunis ◽  
G Dreyfuss
Keyword(s):  
Rna Polymerase Ii ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Uv Light ◽  
Binding Protein ◽  
Gene Replacement ◽  
Yeast Saccharomyces Cerevisiae ◽  
Binding Domains ◽  
Development And Differentiation

The expression of RNA polymerase II transcripts can be regulated at the posttranscriptional level by RNA-binding proteins. Although extensively characterized in metazoans, relatively few RNA-binding proteins have been characterized in the yeast Saccharomyces cerevisiae. Three major proteins are cross-linked by UV light to poly(A)+ RNA in living S. cerevisiae cells. These are the 72-kDa poly(A)-binding protein and proteins of 60 and 50 kDa (S.A. Adam, T.Y. Nakagawa, M.S. Swanson, T. Woodruff, and G. Dreyfuss, Mol. Cell. Biol. 6:2932-2943, 1986). Here, we describe the 60-kDa protein, one of the major poly(A)+ RNA-binding proteins in S. cerevisiae. This protein, PUB1 [for poly(U)-binding protein 1], was purified by affinity chromatography on immobilized poly(rU), and specific monoclonal antibodies to it were produced. UV cross-linking demonstrated that PUB1 is bound to poly(A)+ RNA (mRNA or pre-mRNA) in living cells, and it was detected primarily in the cytoplasm by indirect immunofluorescence. The gene for PUB1 was cloned and sequenced, and the sequence was found to predict a 51-kDa protein with three ribonucleoprotein consensus RNA-binding domains and three glutamine- and asparagine-rich auxiliary domains. This overall structure is remarkably similar to the structures of the Drosophila melanogaster elav gene product, the human neuronal antigen HuD, and the cytolytic lymphocyte protein TIA-1. Each of these proteins has an important role in development and differentiation, potentially by affecting RNA processing. PUB1 was found to be nonessential in S. cerevisiae by gene replacement; however, further genetic analysis should reveal important features of this class of RNA-binding proteins.

scholarly journals The structural basis for RNA selectivity by the IMP family of RNA-binding proteins

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeetayu Biswas ◽  
Vivek L. Patel ◽  
Varun Bhaskar ◽  
Jeffrey A. Chao ◽  
Robert H. Singer ◽  
...  
Keyword(s):  
Neural Development ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Stability ◽  
Underlying Mechanism ◽  
Structural Basis ◽  
General Mechanism ◽  
Binding Domains ◽  
Variable Loops

Abstract The IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.

scholarly journals CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lizhen Chen ◽  
Zhijie Liu ◽  
Bing Zhou ◽  
Chaoliang Wei ◽  
Yu Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Alternative Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Axon Regeneration ◽  
Rna Binding Proteins ◽  
Mrna Isoforms ◽  
C Elegans ◽  
Mrna Targets

Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE Syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. Further, mRNAs for several Syntaxins show CELF2 dependent regulation. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.

scholarly journals KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Dustin Haskell ◽  
Anna Zinovyeva
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulate Gene Expression ◽  
C Elegans ◽  
Binding Domains ◽  
Kh Domain ◽  
Regulate Gene

Abstract MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate their activities and the precise mechanisms of this coordination are not well understood. RBPs often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa-1 and asd-2, genetically interacted with all of the miRNA mutants tested, whereas other KH domain genes showed genetic interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

scholarly journals A nuclear localization domain in the hnRNP A1 protein.

1995 ◽  
Vol 129 (3) ◽  
pp. 551-560 ◽  
Author(s):  
H Siomi ◽  
G Dreyfuss
Keyword(s):  
Nuclear Localization ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Motif ◽  
Hnrnp A1 ◽  
Binding Domains ◽  
Rich Domain ◽  
Localization Domain ◽  
Hnrnp Proteins

The heterogeneous nuclear RNP (hnRNP) A1 protein is one of the major pre-mRNA/mRNA binding proteins in eukaryotic cells and one of the most abundant proteins in the nucleus. It is localized to the nucleoplasm and it also shuttles between the nucleus and the cytoplasm. The amino acid sequence of A1 contains two RNP motif RNA-binding domains (RBDs) at the amino terminus and a glycine-rich domain at the carboxyl terminus. This configuration, designated 2x RBD-Gly, is representative of perhaps the largest family of hnRNP proteins. Unlike most nuclear proteins characterized so far, A1 (and most 2x RBD-Gly proteins) does not contain a recognizable nuclear localization signal (NLS). We have found that a segment of ca. 40 amino acids near the carboxyl end of the protein (designated M9) is necessary and sufficient for nuclear localization; attaching this segment to the bacterial protein beta-galactosidase or to pyruvate kinase completely localized these otherwise cytoplasmic proteins to the nucleus. The RBDs and another RNA binding motif found in the glycine-rich domain, the RGG box, are not required for A1 nuclear localization. M9 is a novel type of nuclear localization domain as it does not contain sequences similar to classical basic-type NLS. Interestingly, sequences similar to M9 are found in other nuclear RNA-binding proteins including hnRNP A2.

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