scholarly journals Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1554 ◽  
Author(s):  
Maria Patrizia Somma ◽  
Evgeniya N. Andreyeva ◽  
Gera A. Pavlova ◽  
Claudia Pellacani ◽  
Elisabetta Bucciarelli ◽  
...  
Keyword(s):  
Evolutionary Process ◽  
Splicing Factors ◽  
Insufficient Data ◽  
Primary Role ◽  
Interphase Nuclei ◽  
Protein Databases ◽  
Moonlighting Proteins ◽  
Bona Fide ◽  
Cellular Compartments ◽  
Moonlighting Functions

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions.

scholarly journals Can bioinformatics help in the identification of moonlighting proteins?

2014 ◽  
Vol 42 (6) ◽  
pp. 1692-1697 ◽  
Author(s):  
Sergio Hernández ◽  
Alejandra Calvo ◽  
Gabriela Ferragut ◽  
Luís Franco ◽  
Antoni Hermoso ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Structural Information ◽  
Evolutionary Relationship ◽  
Evolutionary Process ◽  
Main Function ◽  
Remote Homology ◽  
Functional Sites ◽  
Protein Protein Interaction ◽  
Moonlighting Proteins ◽  
Moonlighting Functions

Protein multitasking or moonlighting is the capability of certain proteins to execute two or more unique biological functions. This ability to perform moonlighting functions helps us to understand one of the ways used by cells to perform many complex functions with a limited number of genes. Usually, moonlighting proteins are revealed experimentally by serendipity, and the proteins described probably represent just the tip of the iceberg. It would be helpful if bioinformatics could predict protein multifunctionality, especially because of the large amounts of sequences coming from genome projects. In the present article, we describe several approaches that use sequences, structures, interactomics and current bioinformatics algorithms and programs to try to overcome this problem. The sequence analysis has been performed: (i) by remote homology searches using PSI-BLAST, (ii) by the detection of functional motifs, and (iii) by the co-evolutionary relationship between amino acids. Programs designed to identify functional motifs/domains are basically oriented to detect the main function, but usually fail in the detection of secondary ones. Remote homology searches such as PSI-BLAST seem to be more versatile in this task, and it is a good complement for the information obtained from protein–protein interaction (PPI) databases. Structural information and mutation correlation analysis can help us to map the functional sites. Mutation correlation analysis can be used only in very restricted situations, but can suggest how the evolutionary process of the acquisition of the second function took place.

scholarly journals Moonlighting Proteins: The Case of the Hexokinases

2021 ◽  
Vol 8 ◽  
Author(s):  
Carolina Rodríguez-Saavedra ◽  
Luis Enrique Morgado-Martínez ◽  
Andrés Burgos-Palacios ◽  
Beatriz King-Díaz ◽  
Montserrat López-Coria ◽  
...  
Keyword(s):  
Glucose Sensor ◽  
Conformational State ◽  
Product Concentration ◽  
Profound Impact ◽  
Wide Range ◽  
Range Of Functions ◽  
Moonlighting Proteins ◽  
Regulation Mechanisms ◽  
Metabolic Activities ◽  
Moonlighting Functions

Moonlighting proteins are defined as proteins with two or more functions that are unrelated and independent to each other, so that inactivation of one of them should not affect the second one and vice versa. Intriguingly, all the glycolytic enzymes are described as moonlighting proteins in some organisms. Hexokinase (HXK) is a critical enzyme in the glycolytic pathway and displays a wide range of functions in different organisms such as fungi, parasites, mammals, and plants. This review discusses HXKs moonlighting functions in depth since they have a profound impact on the responses to nutritional, environmental, and disease challenges. HXKs’ activities can be as diverse as performing metabolic activities, as a gene repressor complexing with other proteins, as protein kinase, as immune receptor and regulating processes like autophagy, programmed cell death or immune system responses. However, most of those functions are particular for some organisms while the most common moonlighting HXK function in several kingdoms is being a glucose sensor. In this review, we also analyze how different regulation mechanisms cause HXK to change its subcellular localization, oligomeric or conformational state, the response to substrate and product concentration, and its interactions with membrane, proteins, or RNA, all of which might impact the HXK moonlighting functions.

scholarly journals An evolutionary perspective on protein moonlighting

2014 ◽  
Vol 42 (6) ◽  
pp. 1684-1691 ◽  
Author(s):  
Shelley D. Copley
Keyword(s):  
Point Mutations ◽  
Optimal Solution ◽  
Gene Encoding ◽  
Genetic Changes ◽  
Moonlighting Protein ◽  
History Of ◽  
Moonlighting Proteins ◽  
Ultimate Outcome ◽  
Moonlighting Functions ◽  
Population Effects

Moonlighting proteins serve one or more novel functions in addition to their canonical roles. Moonlighting functions arise when an adventitious interaction between a protein and a new partner improves fitness of the organism. Selective pressure for improvement in the new function can result in two alternative outcomes. The gene encoding the newly bifunctional protein may duplicate and diverge so as to encode two proteins, each of which serves only one function. Alternatively, genetic changes that minimize adaptive conflict between the two functions and/or improve control over the time and place at which each function is served can lead to a moonlighting protein. Importantly, genetic changes that enhance a moonlighting function can occur in the gene encoding the moonlighting protein itself, in a gene that affects the structure of its new partner or in a gene encoding a transcription factor that controls expression of either partner. The evolutionary history of each moonlighting protein is complex, depending on the stochastic occurrence of genetic changes such as gene duplication and point mutations, and the effects of those changes on fitness. Population effects, particularly loss of promising individuals due to random genetic drift, also play a role in the emergence of a moonlighting protein. The ultimate outcome is not necessarily the ‘optimal’ solution to the problem of serving two functions, but may be ‘good enough’ so that fitness becomes limited by some other function.

Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?

2015 ◽  
Vol 396 (5) ◽  
pp. 523-537 ◽  
Author(s):  
Thomas Hildebrandt ◽  
Johannes Knuesting ◽  
Carsten Berndt ◽  
Bruce Morgan ◽  
Renate Scheibe
Keyword(s):  
Hydrogen Peroxide ◽  
Metabolic Flux ◽  
Pentose Phosphate ◽  
Nitrogen Species ◽  
Adaptive Responses ◽  
Cellular Functions ◽  
Cellular Targets ◽  
Catalytic Cysteine ◽  
Cellular Compartments ◽  
Moonlighting Functions

Abstract Cytosolic glyceraldehyde 3-phosphate dehydrogenase (GAPDH, E.C. 1.2.1.12) is present in all organisms and catalyzes the oxidation of triose phosphate during glycolysis. GAPDH is one of the most prominent cellular targets of oxidative modifications when reactive oxygen and nitrogen species are formed during metabolism and under stress conditions. GAPDH harbors a strictly conserved catalytic cysteine, which is susceptible to a variety of thiol modifications, including S-sulfenylation, S-glutathionylation, S-nitrosylation, and S-sulfhydration. Upon reversible oxidative thiol modification of GAPDH, glycolysis is inhibited leading to a diversion of metabolic flux through the pentose-phosphate cycle to increase NADPH production. Furthermore, oxidized GAPDH may adopt new functions in different cellular compartments including the nucleus, as well as in new microcompartments associated with the cytoskeleton, mitochondria and plasma membrane. This review focuses on the recently discovered mechanism underlying the eminent reactivity between GAPDH and hydrogen peroxide and the subsequent redox-dependent moonlighting functions discriminating between the induction either of adaptive responses and adjustment of metabolism or of cell death in yeast, plants, and mammals. In light of the summarized results, cytosolic GAPDH might function as a sensor for redox signals and an information hub to transduce these signals for appropriate responses.

scholarly journals The Expanding Landscape of Moonlighting Proteins in Yeasts

2016 ◽  
Vol 80 (3) ◽  
pp. 765-777 ◽  
Author(s):  
Carlos Gancedo ◽  
Carmen-Lisset Flores ◽  
Juana M. Gancedo
Keyword(s):  
Dna Repair ◽  
Experimental Evidence ◽  
Gene Fusion ◽  
Genetic Manipulation ◽  
Biological Processes ◽  
Multifunctional Proteins ◽  
Moonlighting Proteins ◽  
Moonlighting Functions

SUMMARYMoonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

scholarly journals Magi-1c

2001 ◽  
Vol 153 (5) ◽  
pp. 1127-1132 ◽  
Author(s):  
Laure Strochlic ◽  
Annie Cartaud ◽  
Valérie Labas ◽  
Werner Hoch ◽  
Jean Rossier ◽  
...  
Keyword(s):  
Postsynaptic Membrane ◽  
Primary Role ◽  
Cross Link ◽  
Adult Rat ◽  
Molecular Events ◽  
The Central Nervous System ◽  
Bona Fide ◽  
Receptor Clusters ◽  
Postsynaptic Differentiation

The muscle-specific receptor tyrosine kinase (MuSK) forms part of a receptor complex, activated by nerve-derived agrin, that orchestrates the differentiation of the neuromuscular junction (NMJ). The molecular events linking MuSK activation with postsynaptic differentiation are not fully understood. In an attempt to identify partners and/or effectors of MuSK, cross-linking and immunopurification experiments were performed in purified postsynaptic membranes from the Torpedo electrocyte, a model system for the NMJ. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis was conducted on both cross-link products, and on the major peptide coimmunopurified with MuSK; this analysis identified a polypeptide corresponding to the COOH-terminal fragment of membrane-associated guanylate kinase (MAGUK) with inverted domain organization (MAGI)-1c. A bona fide MAGI-1c (150 kD) was detected by Western blotting in the postsynaptic membrane of Torpedo electrocytes, and in a high molecular mass cross-link product of MuSK. Immunofluorescence experiments showed that MAGI-1c is localized specifically at the adult rat NMJ, but is absent from agrin-induced acetylcholine receptor clusters in myotubes in vitro. In the central nervous system, MAGUKs play a primary role as scaffolding proteins that organize cytoskeletal signaling complexes at excitatory synapses. Our data suggest that a protein from the MAGUK family is involved in the MuSK signaling pathway at the vertebrate NMJ.

scholarly journals ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs

2005 ◽  
Vol 169 (5) ◽  
pp. 745-753 ◽  
Author(s):  
Patrice Vitali ◽  
Eugenia Basyuk ◽  
Elodie Le Meur ◽  
Edouard Bertrand ◽  
Françoise Muscatelli ◽  
...  
Keyword(s):  
Rna Editing ◽  
Serotonin Receptor ◽  
Small Nucleolar Rnas ◽  
Ribonucleoprotein Particle ◽  
Subcellular Targeting ◽  
Adenosine Deaminases ◽  
Bona Fide ◽  
Cellular Compartments ◽  
Nucleolar Rna ◽  
Nucleolar Rnas

Posttranscriptional, site-specific adenosine to inosine (A-to-I) base conversions, designated as RNA editing, play significant roles in generating diversity of gene expression. However, little is known about how and in which cellular compartments RNA editing is controlled. Interestingly, the two enzymes that catalyze RNA editing, adenosine deaminases that act on RNA (ADAR) 1 and 2, have recently been demonstrated to dynamically associate with the nucleolus. Moreover, we have identified a brain-specific small RNA, termed MBII-52, which was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2′-O-methylation. Through the subcellular targeting of minigenes that contain natural editing sites, we show that ADAR2- but not ADAR1-mediated RNA editing occurs in the nucleolus. We also demonstrate that MBII-52 forms a bona fide small nucleolar ribonucleoprotein particle that specifically decreases the efficiency of RNA editing by ADAR2 at the targeted C-site. Our data are consistent with a model in which C/D small nucleolar RNA might play a role in the regulation of RNA editing.

scholarly journals A variational approach to niche construction

2018 ◽  
Vol 15 (141) ◽  
pp. 20170685 ◽  
Author(s):  
Axel Constant ◽  
Maxwell J. D. Ramstead ◽  
Samuel P. L. Veissière ◽  
John O. Campbell ◽  
Karl J. Friston
Keyword(s):  
Variational Approach ◽  
Evolutionary Biology ◽  
Niche Construction ◽  
Evolutionary Process ◽  
Energy Principle ◽  
Evolutionary Trajectory ◽  
Free Energy Principle ◽  
Evolutionary Force ◽  
Bona Fide ◽  
Scientific Fields

In evolutionary biology, niche construction is sometimes described as a genuine evolutionary process whereby organisms, through their activities and regulatory mechanisms, modify their environment such as to steer their own evolutionary trajectory, and that of other species. There is ongoing debate, however, on the extent to which niche construction ought to be considered a bona fide evolutionary force, on a par with natural selection. Recent formulations of the variational free-energy principle as applied to the life sciences describe the properties of living systems, and their selection in evolution, in terms of variational inference. We argue that niche construction can be described using a variational approach. We propose new arguments to support the niche construction perspective, and to extend the variational approach to niche construction to current perspectives in various scientific fields.

Fructose-1,6-bisphosphate aldolase (FBA)–a conserved glycolytic enzyme with virulence functions in bacteria: ‘ill met by moonlight’

2014 ◽  
Vol 42 (6) ◽  
pp. 1792-1795 ◽  
Author(s):  
Fariza Shams ◽  
Neil J. Oldfield ◽  
Karl G. Wooldridge ◽  
David P.J. Turner
Keyword(s):  
Current Knowledge ◽  
Glycolytic Enzyme ◽  
Glycolytic Pathway ◽  
Present Review ◽  
Central Metabolism ◽  
Multifunctional Proteins ◽  
Moonlighting Proteins ◽  
Fructose 1,6 Bisphosphate ◽  
Eukaryotic Organisms ◽  
Moonlighting Functions

Moonlighting proteins constitute an intriguing class of multifunctional proteins. Metabolic enzymes and chaperones, which are often highly conserved proteins in bacteria, archaea and eukaryotic organisms, are among the most commonly recognized examples of moonlighting proteins. Fructose-1,6-bisphosphate aldolase (FBA) is an enzyme involved in the Embden–Meyerhof–Parnas (EMP) glycolytic pathway and in gluconeogenesis. Increasingly, it is also recognized that FBA has additional functions beyond its housekeeping role in central metabolism. In the present review, we summarize the current knowledge of the moonlighting functions of FBA in bacteria.

scholarly journals Huntington’s disease-specific mis-splicing captured by human-mouse intersect-RNA-seq unveils pathogenic effectors and reduced splicing factors

2020 ◽  
Author(s):  
Ainara Elorza ◽  
Yamile Márquez ◽  
Jorge R. Cabrera ◽  
José Luis Sánchez-Trincado ◽  
María Santos-Galindo ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Loss ◽  
Splicing Factors ◽  
Post Mortem ◽  
Rna Seq ◽  
Protein Levels ◽  
Wide Range ◽  
Bona Fide

AbstractDeregulated alternative splicing has been implicated in a wide range of pathologies. Deep RNA-sequencing has revealed global mis-splicing signatures in multiple human diseases; however, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington’s disease (HD) pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the HD-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked effector genes, whose aberrant splicing is associated with decreased protein levels in HD patients and mice. In summary, our intersect-RNA-seq approach unveiled the pathogenic contribution of mis-splicing to HD and could be readily applied to other neurodegenerative diseases for which bona fide animal models are available.

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