scholarly journals Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference

2021 ◽  
Author(s):  
Javier J. Castro Alvarez ◽  
Maxime Revel ◽  
Fabienne Cléard ◽  
Daniel Pauli ◽  
François Karch ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Protein ◽  
Bithorax Complex ◽  
Transcriptional Interference ◽  
Wild Type ◽  
Cellular Functions ◽  
Hox Gene ◽  
Ectopic Activation ◽  
Eukaryotic Genomes ◽  
Interference Mechanism

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3’ end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where in wild-type embryos, it acts on the Hox gene, abd-A located immediately downstream of it. The CNS specificity is achieved through a 3’ extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3’ extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.

scholarly journals Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009843
Author(s):  
Javier J. Castro Alvarez ◽  
Maxime Revel ◽  
Judit Carrasco ◽  
Fabienne Cléard ◽  
Daniel Pauli ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Protein ◽  
Bithorax Complex ◽  
Transcriptional Interference ◽  
Wild Type ◽  
Cellular Functions ◽  
Hox Gene ◽  
Ectopic Activation ◽  
Eukaryotic Genomes ◽  
Interference Mechanism

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3’ end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3’ extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3’ extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.

scholarly journals RNA-Binding Protein HuR Regulates Both Mutant and Wild-Type IDH1 in IDH1-Mutated Cancer

2018 ◽  
Vol 17 (2) ◽  
pp. 508-520 ◽  
Author(s):  
Mahsa Zarei ◽  
Shruti Lal ◽  
Ali Vaziri-Gohar ◽  
Kevin O'Hayer ◽  
Venugopal Gunda ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

scholarly journals New Insights into the Interplay between Non-Coding RNAs and RNA-Binding Protein HnRNPK in Regulating Cellular Functions

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Yongjie Xu ◽  
Wei Wu ◽  
Qiu Han ◽  
Yaling Wang ◽  
Cencen Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Genomic Structure ◽  
Rna Binding Protein ◽  
Stem Cell Differentiation ◽  
Cellular Functions ◽  
Non Coding Rnas ◽  
Conserved Gene

The emerging data indicates that non-coding RNAs (ncRNAs) epresent more than the “junk sequences” of the genome. Both miRNAs and long non-coding RNAs (lncRNAs) are involved in fundamental biological processes, and their deregulation may lead to oncogenesis and other diseases. As an important RNA-binding protein (RBP), heterogeneous nuclear ribonucleoprotein K (hnRNPK) is known to regulate gene expression through the RNA-binding domain involved in various pathways, such as transcription, splicing, and translation. HnRNPK is a highly conserved gene that is abundantly expressed in mammalian cells. The interaction of hnRNPK and ncRNAs defines the novel way through which ncRNAs affect the expression of protein-coding genes and form autoregulatory feedback loops. This review summarizes the interactions of hnRNPK and ncRNAs in regulating gene expression at transcriptional and post-transcriptional levels or by changing the genomic structure, highlighting their involvement in carcinogenesis, glucose metabolism, stem cell differentiation, virus infection and other cellular functions. Drawing connections between such discoveries might provide novel targets to control the biological outputs of cells in response to different stimuli.

scholarly journals A yeast RNA-binding protein shuttles between the nucleus and the cytoplasm.

1994 ◽  
Vol 14 (12) ◽  
pp. 8399-8407 ◽  
Author(s):  
J Flach ◽  
M Bossie ◽  
J Vogel ◽  
A Corbett ◽  
T Jinks ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Binding Motifs ◽  
C Terminus ◽  
N Terminus ◽  
Heterogeneous Nuclear Ribonucleoproteins

RNA-binding proteins have been suggested to move in association with RNA as it leaves the nucleus. The NPL3 gene of the yeast Saccharomyces cerevisiae encodes in nuclear protein with consensus RNA-binding motifs and similarity to heterogeneous nuclear ribonucleoproteins and members of the S/R protein family. We show that although Npl3 is located in the nucleus, it can shuttle between nuclei in yeast heterokaryons. In contrast, other nucleus-targeted proteins do not leave the nucleus under similar conditions. Mutants missing the RNA-binding motifs or the N terminus are still capable of shuttling in and out of the nucleus. Npl3 mutants missing the C terminus fail to localize to the nucleus. Overproduction of Npl3 in wild-type cells shows cell growth. This toxicity depends on the presence of series of unique repeats in the N terminus and localization to the nucleus. We suggest that the properties of Npl3 are consistent with it being involved in export of RNAs from the nucleus.

scholarly journals Post-transcriptional regulation of MEK-1 by polyamines through the RNA-binding protein HuR modulating intestinal epithelial apoptosis

2010 ◽  
Vol 426 (3) ◽  
pp. 293-306 ◽  
Author(s):  
Peng-Yuan Wang ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Lan Xiao ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Transcriptional Level ◽  
Intestinal Epithelial ◽  
Cellular Functions ◽  
Mitogen Activated Protein ◽  
Hu Antigen R ◽  
Post Transcriptional Regulation

MEK-1 [MAPK (mitogen-activated protein kinase) kinase-1] is an important signal transducing enzyme that is implicated in many aspects of cellular functions. In the present paper, we report that cellular polyamines regulate MEK-1 expression at the post-transcriptional level through the RNA-binding protein HuR (Hu-antigen R) in IECs (intestinal epithelial cells). Decreasing the levels of cellular polyamines by inhibiting ODC (ornithine decarboxylase) stabilized MEK-1 mRNA and promoted its translation through enhancement of the interaction between HuR and the 3′-untranslated region of MEK-1 mRNA, whereas increasing polyamine levels by ectopic ODC overexpression destabilized the MEK-1 transcript and repressed its translation by reducing the abundance of HuR–MEK-1 mRNA complex; neither intervention changed MEK-1 gene transcription via its promoter. HuR silencing rendered the MEK-1 mRNA unstable and inhibited its translation, thus preventing increases in MEK-1 mRNA and protein in polyamine-deficient cells. Conversely, HuR overexpression increased MEK-1 mRNA stability and promoted its translation. Inhibition of MEK-1 expression by MEK-1 silencing or HuR silencing prevented the increased resistance of polyamine-deficient cells to apoptosis. Moreover, HuR overexpression did not protect against apoptosis if MEK-1 expression was silenced. These results indicate that polyamines destabilize the MEK-1 mRNA and repress its translation by inhibiting the association between HuR and the MEK-1 transcript. Our findings indicate that MEK-1 is a key effector of the HuR-elicited anti-apoptotic programme in IECs.

The wild type RNase L but not mutant laboratory and natural variants suppresses the RNA binding protein, HUR: Effects on cytokine 3′ UTR

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 50
Author(s):  
Latifa Al-Haj ◽  
Wijdan Al-Ahamdi ◽  
Maha Al-Ghamdi ◽  
Maher Al-Saif ◽  
Edward Hitti ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Rnase L ◽  
Wild Type ◽  
Natural Variants

scholarly journals Inactivation of CUG-BP1/CELF1 Causes Growth, Viability, and Spermatogenesis Defects in Mice

2006 ◽  
Vol 27 (3) ◽  
pp. 1146-1157 ◽  
Author(s):  
Chantal Kress ◽  
Carole Gautier-Courteille ◽  
H. Beverley Osborne ◽  
Charles Babinet ◽  
Luc Paillard
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Leydig Cells ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Cell Number ◽  
Pcr Analysis ◽  
Wild Type ◽  
Mammalian Development ◽  
Males And Females

ABSTRACT CUG-BP1/CELF1 is a multifunctional RNA-binding protein involved in the regulation of alternative splicing and translation. To elucidate its role in mammalian development, we produced mice in which the Cugbp1 gene was inactivated by homologous recombination. These Cugbp1 − / − mice were viable, although a significant portion of them did not survive after the first few days of life. They displayed growth retardation, and most Cugbp1 − / − males and females exhibited impaired fertility. Male infertility was more thoroughly investigated. Histological examination of testes from Cugbp1 − / − males showed an arrest of spermatogenesis that occurred at step 7 of spermiogenesis, before spermatid elongation begins, and an increased apoptosis. A quantitative reverse transcriptase PCR analysis showed a decrease of all the germ cell markers tested but not of Sertoli and Leydig markers, suggesting a general decrease in germ cell number. In wild-type testes, CUG-BP1 is expressed in germ cells from spermatogonia to round spermatids and also in Sertoli and Leydig cells. These findings demonstrate that CUG-BP1 is required for completion of spermatogenesis.

scholarly journals A yeast RNA-binding protein shuttles between the nucleus and the cytoplasm

1994 ◽  
Vol 14 (12) ◽  
pp. 8399-8407
Author(s):  
J Flach ◽  
M Bossie ◽  
J Vogel ◽  
A Corbett ◽  
T Jinks ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Binding Motifs ◽  
C Terminus ◽  
N Terminus ◽  
Heterogeneous Nuclear Ribonucleoproteins

RNA-binding proteins have been suggested to move in association with RNA as it leaves the nucleus. The NPL3 gene of the yeast Saccharomyces cerevisiae encodes in nuclear protein with consensus RNA-binding motifs and similarity to heterogeneous nuclear ribonucleoproteins and members of the S/R protein family. We show that although Npl3 is located in the nucleus, it can shuttle between nuclei in yeast heterokaryons. In contrast, other nucleus-targeted proteins do not leave the nucleus under similar conditions. Mutants missing the RNA-binding motifs or the N terminus are still capable of shuttling in and out of the nucleus. Npl3 mutants missing the C terminus fail to localize to the nucleus. Overproduction of Npl3 in wild-type cells shows cell growth. This toxicity depends on the presence of series of unique repeats in the N terminus and localization to the nucleus. We suggest that the properties of Npl3 are consistent with it being involved in export of RNAs from the nucleus.

scholarly journals Post-translational modification control of RNA-binding protein hnRNPK function

Open Biology ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 180239 ◽  
Author(s):  
Yongjie Xu ◽  
Wei Wu ◽  
Qiu Han ◽  
Yaling Wang ◽  
Cencen Li ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Disease States ◽  
Damage Repair ◽  
Cellular Stresses

Heterogeneous nuclear ribonucleoprotein K (hnRNPK), a ubiquitously occurring RNA-binding protein (RBP), can interact with numerous nucleic acids and various proteins and is involved in a number of cellular functions including transcription, translation, splicing, chromatin remodelling, etc. Through its abundant biological functions, hnRNPK has been implicated in cellular events including proliferation, differentiation, apoptosis, DNA damage repair and the stress and immune responses. Thus, it is critical to understand the mechanism of hnRNPK regulation and its downstream effects on cancer and other diseases. A number of recent studies have highlighted that several post-translational modifications (PTMs) possibly play an important role in modulating hnRNPK function. Phosphorylation is the most widely occurring PTM in hnRNPK. For example, in vivo analyses of sites such as S116 and S284 illustrate the purpose of PTM of hnRNPK in altering its subcellular localization and its ability to bind target nucleic acids or proteins. Other PTMs such as methylation, ubiquitination, sumoylation, glycosylation and proteolytic cleavage are increasingly implicated in the regulation of DNA repair, cellular stresses and tumour growth. In this review, we describe the PTMs that impact upon hnRNPK function on gene expression programmes and different disease states. This knowledge is key in allowing us to better understand the mechanism of hnRNPK regulation.

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