Enzymes as RNA-binding proteins: a role for (di)nucleotide-binding domains?

1994 ◽  
Vol 19 (3) ◽  
pp. 101-103 ◽  
Author(s):  
Matthias W. Hentze
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nucleotide Binding ◽  
Binding Domains

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 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.

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

2019 ◽  
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

AbstractThe 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 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 Combinatorial recognition of clustered RNA elements by a multidomain RNA-binding protein, IMP3

2018 ◽  
Author(s):  
Tim Schneider ◽  
Lee-Hsueh Hung ◽  
Masood Aziz ◽  
Anna Wilmen ◽  
Stephanie Thaum ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Binding Domains ◽  
Systematic Strategy ◽  
Rna Elements ◽  
Target Rna

AbstractHow multidomain RNA-binding proteins recognize their specific target sequences, based on a combinatorial code, represents a fundamental unsolved question and has not been studied systematically so far. Here we focus on a prototypical multidomain RNA-binding protein, IMP3 (also called IGF2BP3), which contains six RNA-binding domains (RBDs): four KH and two RRM domains. We have established an integrative systematic strategy, combining single-domain-resolved SELEX-seq, motif-spacing analyses, in vivo iCLIP, functional validation assays, and structural biology. This approach identifies the RNA-binding specificity and RNP topology of IMP3, involving all six RBDs and a cluster of up to five distinct and appropriately spaced CA-rich and GGC-core RNA elements, covering a >100 nucleotide-long target RNA region. Our generally applicable approach explains both specificity and flexibility of IMP3-RNA recognition, providing a paradigm for the function of multivalent interactions with multidomain RNA-binding proteins in gene regulation.

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 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 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.

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