Identification of a novel enhancer that binds Sp1 and contributes to induction of cold-inducible RNA-binding protein (cirp) expression in mammalian cells

The ESCRT protein CHMP2B and the RNA-binding protein TDP-43 are both associated with ALS and FTD. The pathogenicity of CHMP2B has mainly been considered a consequence of autophagy–endolysosomal dysfunction, whereas protein inclusions containing phosphorylated TDP-43 are a pathological hallmark of ALS and FTD. Intriguingly, TDP-43 pathology has not been associated with the FTD-causing CHMP2BIntron5 mutation. In this study, we identify CHMP2B as a modifier of TDP-43–mediated neurodegeneration in a Drosophila screen. Down-regulation of CHMP2B reduces TDP-43 phosphorylation and toxicity in flies and mammalian cells. Surprisingly, although CHMP2BIntron5 causes dramatic autophagy dysfunction, disturbance of autophagy does not alter TDP-43 phosphorylation levels. Instead, we find that inhibition of CK1, but not TTBK1/2 (all of which are kinases phosphorylating TDP-43), abolishes the modifying effect of CHMP2B on TDP-43 phosphorylation. Finally, we uncover that CHMP2B modulates CK1 protein levels by negatively regulating ubiquitination and the proteasome-mediated turnover of CK1. Together, our findings propose an autophagy-independent role and mechanism of CHMP2B in regulating CK1 abundance and TDP-43 phosphorylation.

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

Cells ◽

10.3390/cells8010062 ◽

2019 ◽

Vol 8 (1) ◽

pp. 62 ◽

Cited By ~ 12

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.

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Vaccinia virus double-stranded RNA-binding protein E3 does not interfere with siRNA-mediated gene silencing in mammalian cells

Virus Research ◽

10.1016/j.virusres.2007.01.009 ◽

2007 ◽

Vol 126 (1-2) ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Markus Lantermann ◽

Astrid Schwantes ◽

Katja Sliva ◽

Gerd Sutter ◽

Barbara S. Schnierle

Keyword(s):

Gene Silencing ◽

Vaccinia Virus ◽

Mammalian Cells ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Double Stranded Rna

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A Glycine-rich RNA-binding Protein Mediating Cold-inducible Suppression of Mammalian Cell Growth

The Journal of Cell Biology ◽

10.1083/jcb.137.4.899 ◽

1997 ◽

Vol 137 (4) ◽

pp. 899-908 ◽

Cited By ~ 221

Author(s):

Hiroyuki Nishiyama ◽

Katsuhiko Itoh ◽

Yoshiyuki Kaneko ◽

Masamichi Kishishita ◽

Osamu Yoshida ◽

...

Keyword(s):

Mammalian Cells ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Rna Binding Protein ◽

Structural Similarity ◽

Mouse Fibroblasts ◽

Amino Terminal ◽

Rich Domain

In response to low ambient temperature, mammalian cells as well as microorganisms change various physiological functions, but the molecular mechanisms underlying these adaptations are just beginning to be understood. We report here the isolation of a mouse cold-inducible RNA-binding protein (cirp) cDNA and investigation of its role in cold-stress response of mammalian cells. The cirp cDNA encoded an 18-kD protein consisting of an amino-terminal RNAbinding domain and a carboxyl-terminal glycine-rich domain and exhibited structural similarity to a class of stress-induced RNA-binding proteins found in plants. Immunofluorescence microscopy showed that CIRP was localized in the nucleoplasm of BALB/3T3 mouse fibroblasts. When the culture temperature was lowered from 37 to 32°C, expression of CIRP was induced and growth of BALB/3T3 cells was impaired as compared with that at 37°C. By suppressing the induction of CIRP with antisense oligodeoxynucleotides, this impairment was alleviated, while overexpression of CIRP resulted in impaired growth at 37°C with prolongation of G1 phase of the cell cycle. These results indicate that CIRP plays an essential role in cold-induced growth suppression of mouse fibroblasts. Identification of CIRP may provide a clue to the regulatory mechanisms of cold responses in mammalian cells.

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Posttranscriptional regulation of PAI-1 gene expression

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613396 ◽

2003 ◽

Vol 89 (06) ◽

pp. 959-966 ◽

Cited By ~ 27

Author(s):

Wendy Dlakic ◽

Thomas Gelehrter ◽

Joanne Heaton

Keyword(s):

Plasminogen Activator ◽

Cyclic Nucleotide ◽

Mammalian Cells ◽

Rna Binding ◽

Binding Protein ◽

Embryo Implantation ◽

Rna Binding Protein ◽

Plasminogen Activator Inhibitor ◽

Nucleotide Regulation ◽

Pai 1

SummaryThe plasminogen activator-plasmin cascade is involved in multiple physiological and pathological processes including fibrinolysis, wound healing, fibrosis, angiogenesis, embryo implantation and tumor cell invasion and metastasis. Plasminogen activator-inhibitor type 1 (PAI-1) is the major physiological regulator of plasminogen activation. PAI-1 is expressed in a variety of mammalian cells and is regulated by growth factors, cytokines and hormones, including agents that elevate cAMP levels. Although cyclic nucleotide regulation of PAI-1 is observed in diverse cell types in various species, including human, limited studies have addressed the mechanism of this regulation. Here we review our work on the regulation of PAI-1 mRNA degradation in HTC rat hepatoma cells, describing the cis-acting cAMP-responsive sequence in the transcript and a novel RNA binding protein that interacts with it. Potential mechanisms by which this RNA-binding protein may be involved in cyclic nucleotide regulation of mRNA stability are discussed and cAMP regulation of PAI-1 in other systems is summarized.Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

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