scholarly journals Mamo decodes hierarchical temporal gradients into terminal neuronal fate

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ling-Yu Liu ◽  
Xi Long ◽  
Ching-Po Yang ◽  
Rosa L Miyares ◽  
Ken Sugino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Neuronal Diversity ◽  
Temporal Expression ◽  
Identity Maintenance ◽  
Temporal Gene Expression ◽  
Neuronal Fate ◽  
Mammalian Genes ◽  
Post Transcriptional Regulation

Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α’/β’ mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.

scholarly journals PSDX: A Comprehensive Multi-Omics Association Database of Populus trichocarpa With a Focus on the Secondary Growth in Response to Stresses

2021 ◽  
Vol 12 ◽  
Author(s):  
Huiyuan Wang ◽  
Sheng Liu ◽  
Xiufang Dai ◽  
Yongkang Yang ◽  
Yunjun Luo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcription Initiation ◽  
High Throughput Sequencing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Secondary Growth ◽  
A Genome ◽  
Post Transcriptional Regulation

Populus trichocarpa (P. trichocarpa) is a model tree for the investigation of wood formation. In recent years, researchers have generated a large number of high-throughput sequencing data in P. trichocarpa. However, no comprehensive database that provides multi-omics associations for the investigation of secondary growth in response to diverse stresses has been reported. Therefore, we developed a public repository that presents comprehensive measurements of gene expression and post-transcriptional regulation by integrating 144 RNA-Seq, 33 ChIP-seq, and six single-molecule real-time (SMRT) isoform sequencing (Iso-seq) libraries prepared from tissues subjected to different stresses. All the samples from different studies were analyzed to obtain gene expression, co-expression network, and differentially expressed genes (DEG) using unified parameters, which allowed comparison of results from different studies and treatments. In addition to gene expression, we also identified and deposited pre-processed data about alternative splicing (AS), alternative polyadenylation (APA) and alternative transcription initiation (ATI). The post-transcriptional regulation, differential expression, and co-expression network datasets were integrated into a new P. trichocarpa Stem Differentiating Xylem (PSDX) database, which further highlights gene families of RNA-binding proteins and stress-related genes. The PSDX also provides tools for data query, visualization, a genome browser, and the BLAST option for sequence-based query. Much of the data is also available for bulk download. The availability of PSDX contributes to the research related to the secondary growth in response to stresses in P. trichocarpa, which will provide new insights that can be useful for the improvement of stress tolerance in woody plants.

scholarly journals RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6835
Author(s):  
Jonas Weiße ◽  
Julia Rosemann ◽  
Vanessa Krauspe ◽  
Matthias Kappler ◽  
Alexander W. Eckert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Invasion And Metastasis ◽  
Protein Coding ◽  
Oral Cancers ◽  
Cellular Processes ◽  
Post Transcriptional Regulation

Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.

scholarly journals The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1539 ◽  
Author(s):  
Yogesh Saini ◽  
Jian Chen ◽  
Sonika Patial
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Zinc Finger ◽  
Binding Proteins ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Finger Protein ◽  
Post Transcriptional Regulation

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

scholarly journals The architecture of the human RNA-binding protein regulatory network

2016 ◽  
Author(s):  
Alessandro Quattrone ◽  
Erik Dassi
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Regulatory Network ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Hierarchical Structures ◽  
Systematic Investigation ◽  
Regulatory Structure ◽  
Post Transcriptional Regulation

AbstractRNA-binding proteins (RBPs) are key players of post-transcriptional regulation of gene expression. These proteins influence both cellular physiology and pathology by regulating processes ranging from splicing and polyadenylation to mRNA localization, stability, and translation. To fine-tune the outcome of their regulatory action, RBPs rely on an intricate web of competitive and cooperative interactions. Several studies have described individual interactions of RBPs with RBP mRNAs, suggestive of a RBP-RBP regulatory structure. Here we present the first systematic investigation of this structure, based on a network including almost fifty thousand experimentally determined interactions between RBPs and bound RBP mRNAs.Our analysis identified two features defining the structure of the RBP-RBP regulatory network. What we call “RBP clusters” are groups of densely interconnected RBPs which co-regulate their targets, suggesting a tight control of cooperative and competitive behaviors. “RBP chains”, instead, are hierarchical structures driven by evolutionarily ancient RBPs, which connect the RBP clusters and could in this way provide the flexibility to coordinate the tuning of a broad set of biological processes.The combination of these two features suggests that RBP chains may use the modulation of their RBP targets to coordinately control the different cell programs controlled by the RBP clusters. Under this island-hopping model, the regulatory signal flowing through the chains hops from one RBP cluster to another, implementing elaborate regulatory plans to impact cellular phenotypes. This work thus establishes RBP-RBP interactions as a backbone driving post-transcriptional regulation of gene expression to allow the fine-grained control of RBPs and their targets.

scholarly journals The search for RNA-binding proteins: a technical and interdisciplinary challenge

2021 ◽  
Author(s):  
Jeffrey M. Smith ◽  
Jarrod J. Sandow ◽  
Andrew I. Webb
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Target Validation ◽  
Binding Function ◽  
Technical Features ◽  
Post Transcriptional Regulation ◽  
The Impact

RNA-binding proteins are customarily regarded as important facilitators of gene expression. In recent years, RNA–protein interactions have also emerged as a pervasive force in the regulation of homeostasis. The compendium of proteins with provable RNA-binding function has swelled from the hundreds to the thousands astride the partnership of mass spectrometry-based proteomics and RNA sequencing. At the foundation of these advances is the adaptation of RNA-centric capture methods that can extract bound protein that has been cross-linked in its native environment. These methods reveal snapshots in time displaying an extensive network of regulation and a wealth of data that can be used for both the discovery of RNA-binding function and the molecular interfaces at which these interactions occur. This review will focus on the impact of these developments on our broader perception of post-transcriptional regulation, and how the technical features of current capture methods, as applied in mammalian systems, create a challenging medium for interpretation by systems biologists and target validation by experimental researchers.

scholarly journals Distinct Hypoxia-induced Translational Profiles of Embryonic and Adult-derived Macrophages

2021 ◽  
Author(s):  
Nicholas S. Wilcox ◽  
Timur O. Yarovinsky ◽  
Prakruti Pandya ◽  
Vinod S. Ramgolam ◽  
Albertomaria Moro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Rna Binding ◽  
Environmental Changes ◽  
Rna Binding Proteins ◽  
Fetal Liver ◽  
Affinity Purification ◽  
Regulation Of Gene Expression ◽  
Translation Rate ◽  
Post Transcriptional Regulation

SummaryTissue homeostasis and repair are orchestrated by resident and newly recruited macrophages that alter their gene expression program in response to changes in tissue microenvironment. Embryonic macrophages, such as fetal liver derived macrophages (FLDM) seed the organs, including heart and lung during embryonic development and persist throughout the adult lifetime, while bone marrow-derived macrophages (BMDM) are recruited following an acute perturbation. Transcriptome analyses of FLDM and BMDM identified differences between them at the level of RNA expression, which correlates imperfectly with protein levels. Post-transcriptional regulation by microRNAs (miRNAs) and RNA-binding proteins determines mRNA stability and translation rate and may override transcriptional cues in response to environmental changes, such as hypoxia. To identify distinct features of FLDM and BMDM response to hypoxia at the level of translation, we employed translating ribosome affinity purification (TRAP) to isolate polysomal RNA. RNA-seq profiling of translated RNA identified distinct hypoxia-induced translational signature of BMDM (Ly6e, vimentin and glycolysis-associated enzymes Pgk1, Tpi1, Aldoa, Ldha) and FLDM (chemokines Ccl7 and Ccl2). By translational profiling of BMDM and FLDM with deletion of the RNA-binding protein HuR, we identified transcripts that were dependent on HuR. These findings highlight the importance of HuR and identify its distinct targets for post-transcriptional regulation of gene expression in embryonic vs. adult-derived macrophages.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

scholarly journals C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons

2021 ◽  
Author(s):  
Eun Seon Kim ◽  
Chang Geon Chung ◽  
Jeong Hyang Park ◽  
Byung Su Ko ◽  
Sung Soon Park ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Accumulation ◽  
Heterozygous Mutation ◽  
Pathological Feature ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Drosophila Model ◽  
Post Transcriptional Regulation

Abstract RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP, Staufen, may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS—but not with mutated endogenous NLS—potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/−), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/− is protective. Stau+/− also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD.

scholarly journals Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Mrinmoyee Majumder ◽  
Viswanathan Palanisamy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Regulatory Pathways ◽  
Advantages And Disadvantages ◽  
Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

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