scholarly journals New insights into the regulatory networks of paralogous genes in bacteria

Microbiology ◽  
2010 ◽  
Vol 156 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Mario A. Martínez-Núñez ◽  
Ernesto Pérez-Rueda ◽  
Rosa María Gutiérrez-Ríos ◽  
Enrique Merino
Keyword(s):  
Gene Duplication ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Selection Process ◽  
Dna Supercoiling ◽  
Model Organisms ◽  
Paralogous Genes ◽  
Pubmed Database

Extensive genomic studies on gene duplication in model organisms such as Escherichia coli and Saccharomyces cerevisiae have recently been undertaken. In these models, it is commonly considered that a duplication event may include a transcription factor (TF), a target gene, or both. Following a gene duplication episode, varying scenarios have been postulated to describe the evolution of the regulatory network. However, in most of these, the TFs have emerged as the most important and in some cases the only factor shaping the regulatory network as the organism responds to a natural selection process, in order to fulfil its metabolic needs. Recent findings concerning the regulatory role played by elements other than TFs have indicated the need to reassess these early models. Thus, we performed an exhaustive review of paralogous gene regulation in E. coli and Bacillus subtilis based on published information, available in the NCBI PubMed database and in well-established regulatory databases. Our survey reinforces the notion that despite TFs being the most prominent components shaping the regulatory networks, other elements are also important. These include small RNAs, riboswitches, RNA-binding proteins, sigma factors, protein–protein interactions and DNA supercoiling, which modulate the expression of genes involved in particular metabolic processes or induce a more complex response in terms of the regulatory networks of paralogous genes in an integrated interplay with TFs.

scholarly journals RNA-Centric Approaches to Profile the RNA–Protein Interaction Landscape on Selected RNAs

2021 ◽  
Vol 7 (1) ◽  
pp. 11 ◽  
Author(s):  
André P. Gerber
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Cell Protein ◽  
Transcriptional Regulatory Networks ◽  
Technological Advances

RNA–protein interactions frame post-transcriptional regulatory networks and modulate transcription and epigenetics. While the technological advances in RNA sequencing have significantly expanded the repertoire of RNAs, recently developed biochemical approaches combined with sensitive mass-spectrometry have revealed hundreds of previously unrecognized and potentially novel RNA-binding proteins. Nevertheless, a major challenge remains to understand how the thousands of RNA molecules and their interacting proteins assemble and control the fate of each individual RNA in a cell. Here, I review recent methodological advances to approach this problem through systematic identification of proteins that interact with particular RNAs in living cells. Thereby, a specific focus is given to in vivo approaches that involve crosslinking of RNA–protein interactions through ultraviolet irradiation or treatment of cells with chemicals, followed by capture of the RNA under study with antisense-oligonucleotides and identification of bound proteins with mass-spectrometry. Several recent studies defining interactomes of long non-coding RNAs, viral RNAs, as well as mRNAs are highlighted, and short reference is given to recent in-cell protein labeling techniques. These recent experimental improvements could open the door for broader applications and to study the remodeling of RNA–protein complexes upon different environmental cues and in disease.

scholarly journals The ATXN2 Orthologs CID3 and CID4, Act Redundantly to In-Fluence Developmental Pathways throughout the Life Cycle of Arabidopsis thaliana

2021 ◽  
Vol 22 (6) ◽  
pp. 3068
Author(s):  
Zaira M. López-Juárez ◽  
Laura Aguilar-Henonin ◽  
Plinio Guzmán
Keyword(s):  
Arabidopsis Thaliana ◽  
Life Cycle ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Leaf Growth ◽  
Transcriptome Profiling ◽  
Developmental Pathways ◽  
Model Organisms ◽  
Key Factors

RNA-binding proteins (RBPs) are key elements involved in post-transcriptional regulation. Ataxin-2 (ATXN2) is an evolutionarily conserved RBP protein, whose function has been studied in several model organisms, from Saccharomyces cerevisiae to the Homo sapiens. ATXN2 interacts with poly(A) binding proteins (PABP) and binds to specific sequences at the 3′UTR of target mRNAs to stabilize them. CTC-Interacting Domain3 (CID3) and CID4 are two ATXN2 orthologs present in plant genomes whose function is unknown. In the present study, phenotypical and transcriptome profiling were used to examine the role of CID3 and CID4 in Arabidopsis thaliana. We found that they act redundantly to influence pathways throughout the life cycle. cid3cid4 double mutant showed a delay in flowering time and a reduced rosette size. Transcriptome profiling revealed that key factors that promote floral transition and floral meristem identity were downregulated in cid3cid4 whereas the flowering repressor FLOWERING LOCUS C (FLC) was upregulated. Expression of key factors in the photoperiodic regulation of flowering and circadian clock pathways, were also altered in cid3cid4, as well as the expression of several transcription factors and miRNAs encoding genes involved in leaf growth dynamics. These findings reveal that ATXN2 orthologs may have a role in developmental pathways throughout the life cycle of plants.

The expanding world of metabolic enzymes moonlighting as RNA binding proteins

2021 ◽  
Author(s):  
Nicole J. Curtis ◽  
Constance J. Jeffery
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Molecular Structures ◽  
Intermediary Metabolism ◽  
The Many ◽  
And Function

RNA binding proteins play key roles in many aspects of RNA metabolism and function, including splicing, transport, translation, localization, stability and degradation. Within the past few years, proteomics studies have identified dozens of enzymes in intermediary metabolism that bind to RNA. The wide occurrence and conservation of RNA binding ability across distant branches of the evolutionary tree suggest that these moonlighting enzymes are involved in connections between intermediary metabolism and gene expression that comprise far more extensive regulatory networks than previously thought. There are many outstanding questions about the molecular structures and mechanisms involved, the effects of these interactions on enzyme and RNA functions, and the factors that regulate the interactions. The effects on RNA function are likely to be wider than regulation of translation, and some enzyme–RNA interactions have been found to regulate the enzyme's catalytic activity. Several enzyme–RNA interactions have been shown to be affected by cellular factors that change under different intracellular and environmental conditions, including concentrations of substrates and cofactors. Understanding the molecular mechanisms involved in the interactions between the enzymes and RNA, the factors involved in regulation, and the effects of the enzyme–RNA interactions on both the enzyme and RNA functions will lead to a better understanding of the role of the many newly identified enzyme–RNA interactions in connecting intermediary metabolism and gene expression.

scholarly journals HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Jessica Rea ◽  
Valentina Menci ◽  
Paolo Tollis ◽  
Tiziana Santini ◽  
Alexandros Armaos ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Cell Fate ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Cascade ◽  
Expression Control ◽  
Gene Expression Control

Abstract Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.

scholarly journals RNA–protein interactions: disorder, moonlighting and junk contribute to eukaryotic complexity

Open Biology ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 190096 ◽  
Author(s):  
Anna Balcerak ◽  
Alicja Trebinska-Stryjewska ◽  
Ryszard Konopinski ◽  
Maciej Wakula ◽  
Ewa Anna Grzybowska
Keyword(s):  
Protein Interactions ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Binding Motifs ◽  
Coding Regions ◽  
Regulatory Circuits ◽  
Proteins Interactions

RNA–protein interactions are crucial for most biological processes in all organisms. However, it appears that the complexity of RNA-based regulation increases with the complexity of the organism, creating additional regulatory circuits, the scope of which is only now being revealed. It is becoming apparent that previously unappreciated features, such as disordered structural regions in proteins or non-coding regions in DNA leading to higher plasticity and pliability in RNA–protein complexes, are in fact essential for complex, precise and fine-tuned regulation. This review addresses the issue of the role of RNA–protein interactions in generating eukaryotic complexity, focusing on the newly characterized disordered RNA-binding motifs, moonlighting of metabolic enzymes, RNA-binding proteins interactions with different RNA species and their participation in regulatory networks of higher order.

AU-rich RNA binding proteins in hematopoiesis and leukemogenesis

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5732-5740 ◽  
Author(s):  
Maria Baou ◽  
John D. Norton ◽  
John J. Murphy
Keyword(s):  
Cell Growth ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Growth And Survival ◽  
Hematopoietic Malignancies ◽  
Gene Regulatory

Abstract Posttranscriptional mechanisms are now widely acknowledged to play a central role in orchestrating gene-regulatory networks in hematopoietic cell growth, differentiation, and tumorigenesis. Although much attention has focused on microRNAs as regulators of mRNA stability/translation, recent data have highlighted the role of several diverse classes of AU-rich RNA-binding protein in the regulation of mRNA decay/stabilization. AU-rich elements are found in the 3′-untranslated region of many mRNAs that encode regulators of cell growth and survival, such as cytokines and onco/tumor-suppressor proteins. These are targeted by a burgeoning number of different RNA-binding proteins. Three distinct types of AU-rich RNA binding protein (ARE poly-U–binding degradation factor-1/AUF1, Hu antigen/HuR/HuA/ELAVL1, and the tristetraprolin/ZFP36 family of proteins) are essential for normal hematopoiesis. Together with 2 further AU-rich RNA-binding proteins, nucleolin and KHSRP/KSRP, the functions of these proteins are intimately associated with pathways that are dysregulated in various hematopoietic malignancies. Significantly, all of these AU-rich RNA-binding proteins function via an interconnected network that is integrated with microRNA functions. Studies of these diverse types of RNA binding protein are providing novel insight into gene-regulatory mechanisms in hematopoiesis in addition to offering new opportunities for developing mechanism-based targeted therapeutics in leukemia and lymphoma.

scholarly journals Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Chase A Weidmann ◽  
Chen Qiu ◽  
René M Arvola ◽  
Tzu-Fang Lou ◽  
Jordan Killingsworth ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Recognition ◽  
Recognition Sequence ◽  
Repression Complex ◽  
Neuronal Functions ◽  
Rna Complexes

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.

scholarly journals CLIPreg: Constructing translational regulatory networks from CLIP-, Ribo- and RNA-seq

2021 ◽  
Author(s):  
Baptiste Kerouanton ◽  
Sebastian Schafer ◽  
Lena Ho ◽  
Sonia Chothani ◽  
Owen JL Rackham
Keyword(s):  
Protein Interactions ◽  
Translational Regulation ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Sequencing Data ◽  
Data Types ◽  
Network Resources ◽  
Gene Regulatory

Motivation: The creation and analysis of gene regulatory networks have been the focus of bioinformatic research and underpins much of what is known about gene regulation. However, as a result of a bias in the availability of data-types that are collected, the vast majority of gene regulatory network resources and tools have focused on either transcriptional regulation or protein-protein interactions. This has left other areas of regulation, for instance translational regulation, vastly underrepresented despite them having been shown to play a critical role in both health and disease. Results: In order to address this we have developed CLIPreg, a package that integrates RNA, Ribo and CLIP- sequencing data in order to construct translational regulatory networks coordinated by RNA-binding proteins. This is the first tool of its type to be created, allowing for detailed investigation into a previously unseen layer of regulation.

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