Biological roles of translin and translin-associated factor-X: RNA metabolism comes to the fore

2010 ◽  
Vol 429 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Alessa Jaendling ◽  
Ramsay J. McFarlane
Keyword(s):  
Nucleic Acid ◽  
Cell Biology ◽  
Genome Stability ◽  
Growth Regulation ◽  
Biological Activities ◽  
Biochemical Properties ◽  
Nucleic Acid Metabolism ◽  
Factor X ◽  
Nucleic Acid Binding ◽  
Associated Factor

Translin, and its binding partner protein TRAX (translin-associated factor-X) are a paralogous pair of conserved proteins, which have been implicated in a broad spectrum of biological activities, including cell growth regulation, mRNA processing, spermatogenesis, neuronal development/function, genome stability regulation and carcinogenesis, although their precise role in some of these processes remains unclear. Furthermore, translin (with or without TRAX) has nucleic-acid-binding activity and it is apparent that controlling nucleic acid metabolism and distribution are central to the biological role(s) of this protein and its partner TRAX. More recently, translin and TRAX have together been identified as enhancer components of an RNAi (RNA interference) pathway in at least one organism and this might provide critical insight into the biological roles of this enigmatic partnership. In the present review we discuss the biological and the biochemical properties of these proteins that indicate that they play a central and important role in eukaryotic cell biology.

scholarly journals GraphBind: protein structural context embedded rules learned by hierarchical graph neural networks for recognizing nucleic-acid-binding residues

2021 ◽  
Author(s):  
Ying Xia ◽  
Chun-Qiu Xia ◽  
Xiaoyong Pan ◽  
Hong-Bin Shen
Keyword(s):  
Neural Networks ◽  
Nucleic Acid ◽  
Biological Activities ◽  
New Drugs ◽  
Superior Performance ◽  
Nucleic Acid Binding ◽  
Hierarchical Graph ◽  
Binding Residue ◽  
Binding Residues ◽  
Graph Neural Networks

Abstract Knowledge of the interactions between proteins and nucleic acids is the basis of understanding various biological activities and designing new drugs. How to accurately identify the nucleic-acid-binding residues remains a challenging task. In this paper, we propose an accurate predictor, GraphBind, for identifying nucleic-acid-binding residues on proteins based on an end-to-end graph neural network. Considering that binding sites often behave in highly conservative patterns on local tertiary structures, we first construct graphs based on the structural contexts of target residues and their spatial neighborhood. Then, hierarchical graph neural networks (HGNNs) are used to embed the latent local patterns of structural and bio-physicochemical characteristics for binding residue recognition. We comprehensively evaluate GraphBind on DNA/RNA benchmark datasets. The results demonstrate the superior performance of GraphBind than state-of-the-art methods. Moreover, GraphBind is extended to other ligand-binding residue prediction to verify its generalization capability. Web server of GraphBind is freely available at http://www.csbio.sjtu.edu.cn/bioinf/GraphBind/.

scholarly journals Structural basis for multifunctional roles of human Ints3 C-terminal domain

2020 ◽  
pp. jbc.RA120.016393
Author(s):  
Jian Li ◽  
Xinli Ma ◽  
Surajit Banerjee ◽  
Sankar Baruah ◽  
Nicholas J Schnicker ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Genome Stability ◽  
Double Strand Breaks ◽  
Structural Basis ◽  
Nucleic Acid Binding ◽  
Ataxia Telangiectasia Mutated ◽  
Interacting Protein ◽  
Strand Breaks ◽  
Terminal Domain

Proper repair of damaged DNA is critical for the maintenance of genome stability. A complex composed of Integrator subunit 3 (Ints3), single-stranded DNA-binding protein 1 (SSB1) and SSB-interacting protein 1 (SSBIP1) is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ataxia-telangiectasia mutated (ATM)-dependent signaling pathways. It is known that in this complex the Ints3 N-terminal domain scaffolds SSB1 and SSBIP1. However, the molecular basis for the function of the Ints3 C-terminal domain remains unclear. Here, we present the crystal structure of the Ints3 C-terminal domain, uncovering a HEAT-repeat superhelical fold. Using structure and mutation analysis, we show that the C-terminal domain exists as a stable dimer. A basic groove and a cluster of conserved residues on two opposite sides of the dimer bind single-stranded RNA/DNA (ssRNA/ssDNA) and Integrator complex subunit 6 (Ints6), respectively. Dimerization is required for nucleic acid binding, but not for Ints6 binding. Additionally, in vitro experiments using HEK 293T cells demonstrate that Ints6 interaction is critical for maintaining SSB1 protein level. Taken together, our findings establish the structural basis of a multifunctional Ints3 C-terminal module, allowing us to propose a novel mode of nucleic acid recognition by helical repeat protein and paving the way for future mechanistic studies.

Ribonuclease H2 in health and disease

2014 ◽  
Vol 42 (4) ◽  
pp. 717-725 ◽  
Author(s):  
Martin A.M. Reijns ◽  
Andrew P. Jackson
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Viral Infection ◽  
Genome Stability ◽  
Innate Immune ◽  
Nucleic Acid Metabolism ◽  
Developmental Studies ◽  
Cellular Processes ◽  
Immune Sensing ◽  
Rnase H2

Innate immune sensing of nucleic acids provides resistance against viral infection and is important in the aetiology of autoimmune diseases. AGS (Aicardi–Goutières syndrome) is a monogenic autoinflammatory disorder mimicking in utero viral infection of the brain. Phenotypically and immunologically, it also exhibits similarities to SLE (systemic lupus erythaematosus). Three of the six genes identified to date encode components of the ribonuclease H2 complex. As all six encode enzymes involved in nucleic acid metabolism, it is thought that pathogenesis involves the accumulation of nucleic acids to stimulate an inappropriate innate immune response. Given that AGS is a monogenic disorder with a defined molecular basis, we use it as a model for common autoimmune disease to investigate cellular processes and molecular pathways responsible for nucleic-acid-mediated autoimmunity. These investigations have also provided fundamental insights into the biological roles of the RNase H2 endonuclease enzyme. In the present article, we describe how human RNase H2 and its role in AGS were first identified, and give an overview of subsequent structural, biochemical, cellular and developmental studies of this enzyme. These investigations have culminated in establishing this enzyme as a key genome-surveillance enzyme required for mammalian genome stability.

Introduction

1978 ◽  
Vol 36 (3) ◽  
pp. 543-544
Author(s):  
W. Bernard
Keyword(s):  
Molecular Weight ◽  
Electron Microscope ◽  
Nucleic Acid ◽  
Gene Mapping ◽  
Molecular Genetics ◽  
Cell Biology ◽  
Gene Activity ◽  
Close Connection ◽  
Basic Information ◽  
Simple Systems

In comparison to many other fields of ultrastructural research in Cell Biology, the successful exploration of genes and gene activity with the electron microscope in higher organisms is a late conquest. Nucleic acid molecules of Prokaryotes could be successfully visualized already since the early sixties, thanks to the Kleinschmidt spreading technique - and much basic information was obtained concerning the shape, length, molecular weight of viral, mitochondrial and chloroplast nucleic acid. Later, additonal methods revealed denaturation profiles, distinction between single and double strandedness and the use of heteroduplexes-led to gene mapping of relatively simple systems carried out in close connection with other methods of molecular genetics.

Snapshot blotting: The transfer of nucleic acids and nucleoprotein complexes from electrophoresis gels to EM grids

1992 ◽  
Vol 50 (1) ◽  
pp. 762-763
Author(s):  
Stephen D. Jett
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Nucleic Acid Binding ◽  
Mobility Shift ◽  
Carbon Coated ◽  
Nucleoprotein Complexes ◽  
Mobility Shift Assay ◽  
Protein Nucleic Acid ◽  
Gel Mobility Shift ◽  
Nucleic Acid Interactions

The electrophoresis gel mobility shift assay is a popular method for the study of protein-nucleic acid interactions. The binding of proteins to DNA is characterized by a reduction in the electrophoretic mobility of the nucleic acid. Binding affinity, stoichiometry, and kinetics can be obtained from such assays; however, it is often desirable to image the various species in the gel bands using TEM. Present methods for isolation of nucleoproteins from gel bands are inefficient and often destroy the native structure of the complexes. We have developed a technique, called “snapshot blotting,” by which nucleic acids and nucleoprotein complexes in electrophoresis gels can be electrophoretically transferred directly onto carbon-coated grids for TEM imaging.

EFFECT OF L-CYSTEINE ON α-AMYLASE PRODUCTION AND NUCLEIC ACID METABOLISM IN BACILLUS SUBTILIS

1963 ◽  
Vol 9 (3) ◽  
pp. 337-341 ◽  
Author(s):  
MICHIO OISHI ◽  
SHIGERU KITAYAMA ◽  
HAJIME TAKAHASHI ◽  
BUNJI MARUO
Keyword(s):  
Bacillus Subtilis ◽  
Nucleic Acid ◽  
Acid Metabolism ◽  
Nucleic Acid Metabolism ◽  
Amylase Production
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