scholarly journals RaPID Analysis of Cytomegalovirus of Long Noncoding RNA Binding Proteins

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Jessica E. Lee ◽  
Caroline Kulesza
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rapid Analysis

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 Evolution of the Small Family of Alternative Splicing Modulators Nuclear Speckle RNA-Binding Proteins in Plants

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 207 ◽  
Author(s):  
Leandro Lucero ◽  
Jeremie Bazin ◽  
Johan Rodriguez Melo ◽  
Fernando Ibañez ◽  
Martín D. Crespi ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Medicago Truncatula ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nodule Development ◽  
Nuclear Speckle ◽  
Symbiotic Nodule

RNA-Binding Protein 1 (RBP1) was first identified as a protein partner of the long noncoding RNA (lncRNA) ENOD40 in Medicago truncatula, involved in symbiotic nodule development. RBP1 is localized in nuclear speckles and can be relocalized to the cytoplasm by the interaction with ENOD40. The two closest homologs to RBP1 in Arabidopsis thaliana were called Nuclear Speckle RNA-binding proteins (NSRs) and characterized as alternative splicing modulators of specific mRNAs. They can recognize in vivo the lncRNA ALTERNATIVE SPLICING COMPETITOR (ASCO) among other lncRNAs, regulating lateral root formation. Here, we performed a phylogenetic analysis of NSR/RBP proteins tracking the roots of the family to the Embryophytes. Strikingly, eudicots faced a reductive trend of NSR/RBP proteins in comparison with other groups of flowering plants. In Medicago truncatula and Lotus japonicus, their expression profile during nodulation and in specific regions of the symbiotic nodule was compared to that of the lncRNA ENOD40, as well as to changes in alternative splicing. This hinted at distinct and specific roles of each member during nodulation, likely modulating the population of alternatively spliced transcripts. Our results establish the basis to guide future exploration of NSR/RBP function in alternative splicing regulation in different developmental contexts along the plant lineage.

scholarly journals Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers

2019 ◽  
Vol 20 (16) ◽  
pp. 3926 ◽  
Author(s):  
Xing Zhao ◽  
Yujie Cai ◽  
Jianzhen Xu
Keyword(s):  
Noncoding Rna ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cancer Development ◽  
Circular Rnas ◽  
Open Questions ◽  
Circular Configuration ◽  
And Function

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed.

scholarly journals Capturing RNA–protein interaction via CRUIS

2020 ◽  
Vol 48 (9) ◽  
pp. e52-e52 ◽  
Author(s):  
Ziheng Zhang ◽  
Weiping Sun ◽  
Tiezhu Shi ◽  
Pengfei Lu ◽  
Min Zhuang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Dna Damage ◽  
Protein Interactions ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Living Cells ◽  
Innovative Methods ◽  
Rna Biology

Abstract No RNA is completely naked from birth to death. RNAs function with and are regulated by a range of proteins that bind to them. Therefore, the development of innovative methods for studying RNA–protein interactions is very important. Here, we developed a new tool, the CRISPR-based RNA-United Interacting System (CRUIS), which captures RNA–protein interactions in living cells by combining the power of CRISPR and PUP-IT, a novel proximity targeting system. In CRUIS, dCas13a is used as a tracker to target specific RNAs, while proximity enzyme PafA is fused to dCas13a to label the surrounding RNA-binding proteins, which are then identified by mass spectrometry. To identify the efficiency of CRUIS, we employed NORAD (Noncoding RNA activated by DNA damage) as a target, and the results show that a similar interactome profile of NORAD can be obtained as by using CLIP (crosslinking and immunoprecipitation)-based methods. Importantly, several novel NORAD RNA-binding proteins were also identified by CRUIS. The use of CRUIS facilitates the study of RNA–protein interactions in their natural environment, and provides new insights into RNA biology.

scholarly journals Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

2015 ◽  
Vol 210 (4) ◽  
pp. 529-539 ◽  
Author(s):  
Sven Hennig ◽  
Geraldine Kong ◽  
Taro Mannen ◽  
Agata Sadowska ◽  
Simon Kobelke ◽  
...  
Keyword(s):  
Phase Transitions ◽  
Liquid Phase ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Rna Binding Proteins ◽  
Low Complexity ◽  
Nuclear Body ◽  
Interactome Network

Prion-like domains (PLDs) are low complexity sequences found in RNA binding proteins associated with the neurodegenerative disorder amyotrophic lateral sclerosis. Recently, PLDs have been implicated in mediating gene regulation via liquid-phase transitions that drive ribonucleoprotein granule assembly. In this paper, we report many PLDs in proteins associated with paraspeckles, subnuclear bodies that form around long noncoding RNA. We mapped the interactome network of paraspeckle proteins, finding enrichment of PLDs. We show that one protein, RBM14, connects key paraspeckle subcomplexes via interactions mediated by its PLD. We further show that the RBM14 PLD, as well as the PLD of another essential paraspeckle protein, FUS, is required to rescue paraspeckle formation in cells in which their endogenous counterpart has been knocked down. Similar to FUS, the RBM14 PLD also forms hydrogels with amyloid-like properties. These results suggest a role for PLD-mediated liquid-phase transitions in paraspeckle formation, highlighting this nuclear body as an excellent model system for understanding the perturbation of such processes in neurodegeneration.

scholarly journals EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression

2016 ◽  
Vol 113 (12) ◽  
pp. 3221-3226 ◽  
Author(s):  
Nara Lee ◽  
Therese A. Yario ◽  
Jessica S. Gao ◽  
Joan A. Steitz
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Lytic Replication ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Mrna Levels ◽  
Binding Studies

Epstein–Barr virus (EBV) produces a highly abundant noncoding RNA called EBV-encoded RNA 2 (EBER2) that interacts indirectly with the host transcription factor paired box protein 5 (PAX5) to regulate viral latent membrane protein 1/2 (LMP1/2) gene expression as well as EBV lytic replication. To identify intermediary proteins, we isolated EBER2–PAX5-containing complexes and analyzed the protein components by mass spectrometry. The top candidates include three host proteins splicing factor proline and glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and RNA binding motif protein 14 (RBM14), all reported to be components of nuclear bodies called paraspeckles. In vivo RNA–protein crosslinking indicates that SFPQ and RBM14 contact EBER2 directly. Binding studies using recombinant proteins demonstrate that SFPQ and NONO associate with PAX5, potentially bridging its interaction with EBER2. Similar to EBER2 or PAX5 depletion, knockdown of any of the three host RNA-binding proteins results in the up-regulation of viral LMP2A mRNA levels, supporting a physiologically relevant interaction of these newly identified factors with EBER2 and PAX5. Identification of these EBER2-interacting proteins enables the search for cellular noncoding RNAs that regulate host gene expression in a manner similar to EBER2.

scholarly journals A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells

2015 ◽  
Author(s):  
Ailone Tichon ◽  
Noa Gil ◽  
Yoav Lubelsky ◽  
Tal Havkin Solomon ◽  
Doron Lemze ◽  
...  
Keyword(s):  
Cell Division ◽  
Human Genome ◽  
Chromosome Segregation ◽  
Binding Sites ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Levels ◽  
Pumilio Proteins

AbstractThousands of long noncoding RNA (lncRNA) genes are encoded in the human genome, and hundreds of them are evolutionary conserved, but their functions and modes of action remain largely obscure. Particularly enigmatic lncRNAs are those that are exported to the cytoplasm, including NORAD – an abundant and highly conserved cytoplasmic lncRNA. Most of the sequence of NORAD is comprised of repetitive units that together contain at least 17 functional binding sites for the two Pumilio homologs in mammals. Through binding to PUM1 and PUM2, NORAD modulates the mRNA levels of their targets, which are enriched for genes involved in chromosome segregation during cell division. Our results suggest that some cytoplasmic lncRNAs function by modulating the activities of RNA binding proteins, an activity which positions them at key junctions of cellular signaling pathways.

scholarly journals Long Noncoding RNA UCA1 Promotes Glutamine-Driven Anaplerosis of Bladder Cancer by Interacting With hnRNP I/L to Upregulate GPT2 Expression

2020 ◽  
Author(s):  
Hua Zhao ◽  
Wenjing Wu ◽  
Xu Li ◽  
Wei Chen
Keyword(s):  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Metabolic Flux ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Luciferase Reporter ◽  
Flux Analysis

Abstract Background: Glutamine-driven anaplerosis maintains the tricarboxylic acid (TCA) cycle by replenishing its carbon source of intermediates with the glutamine-derived carbons in cancer cells. Long noncoding RNA urothelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remains elusive. Methods: The mechanism of UCA1 bound to and facilitated the combination of hnRNP I/L to the promoter of GPT2 gene was investigated by RNA pulldown, qRT-PCR, western blot, dual luciferase reporter assays, immunohistochemical staining, chromatin immunoprecipitation and chromatin isolation by RNA purification. Metabolomics analysis and metabolic flux analysis were conducted to assess the effects of UCA1, hnRNP I/L, and GPT2 on metabolic reprogramming of BLCA.Results: We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and viability of BLCA cells. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2) gene, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1, hnRNP I/L, and GPT2 on metabolism and proliferation via glutamine-driven anaplerosis in BLCA cells. Conclusions: Our study reveals the critical mechanism by which UCA1 forms a functional UCA1-hnRNP I/L complex that upregulates GPT2 expression to promote glutamine-driven TCA cycle anaplerosis, providing novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.

scholarly journals The Developmentally Active and Stress-Inducible Noncoding hsrω Gene Is a Novel Regulator of Apoptosis in Drosophila

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 831-852 ◽  
Author(s):  
Moushami Mallik ◽  
Subhash C. Lakhotia
Keyword(s):  
Cell Death ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genetic Interaction ◽  
Apoptotic Cell ◽  
Cell Death Pathway ◽  
Apoptosis Protein ◽  
Multiple Paths

The large nucleus limited noncoding hsrω-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsrω transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsrω transcripts suppressed JNK activation. In addition, hsrω-RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. Suppression of induced cell death following depletion of hsrω transcripts was abrogated when the DIAP1-RNAi transgene was coexpressed. Our results suggest that the hsrω transcripts regulate cellular levels of DIAP1 via the hnRNP Hrb57A, which physically interacts with DIAP1, and any alteration in levels of the hsrω transcripts in eye disc cells enhances association between these two proteins. Our studies thus reveal a novel regulatory role of the hsrω noncoding RNA on the apoptotic cell death cascade through multiple paths. These observations add to the diversity of regulatory functions that the large noncoding RNAs carry out in the cells' life.

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