scholarly journals Targeted deletion of the RNA-binding protein Caprin1 leads to progressive hearing loss and impairs recovery from noise exposure in mice.

2021 ◽  
Author(s):  
Lisa S Nolan ◽  
Jing Chen ◽  
Ana Claudia Goncalves ◽  
Anwen Bullen ◽  
Karen P Steel ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granules ◽  
Auditory Brainstem Responses ◽  
Progressive Hearing Loss ◽  
Granule Formation ◽  
Deficient Mice

Cell cycle associated protein 1 (Caprin1) is an RNA-binding protein that can regulate the cellular post-transcriptional response to stress. It is a component of both stress granules and neuronal RNA granules and is implicated in neurodegenerative disease, synaptic plasticity and long-term memory formation. Our previous work suggested that Caprin1 also plays a role in the response of the cochlea to stress. Here, targeted inner ear-deletion of Caprin1 in mice leads to an early onset, progressive hearing loss. Auditory brainstem responses from Caprin1-deficient mice show reduced thresholds, with a significant reduction in wave-I amplitudes compared to wildtype. Whilst hair cell structure and numbers were normal, the inner hair cell-spiral ganglion neuron (IHC-SGN) synapse revealed abnormally large post-synaptic GluA2 receptor puncta, a defect consistent with the observed wave-I reduction. Unlike wildtype mice, mild-noise induced hearing threshold shifts in Caprin1-deficient mice did not recover. Oxidative stress triggered TIA-1/HuR positive stress granule formation in ex-vivo cochlear explants from Caprin1-deficient mice, showing that stress granules could still be induced. Taken together, these findings suggest that Caprin1 plays a key role in maintenance of auditory function, where it regulates the normal status of the IHC-SGN synapse.

scholarly journals Cytoplasmic Granule Formation and Translational Inhibition of Nodaviral RNAs in the Absence of the Double-Stranded RNA Binding Protein B2

2013 ◽  
Vol 87 (24) ◽  
pp. 13409-13421 ◽  
Author(s):  
J. E. Petrillo ◽  
P. A. Venter ◽  
J. R. Short ◽  
R. Gopal ◽  
S. Deddouche ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cytoplasmic Granule ◽  
Granule Formation ◽  
Double Stranded Rna ◽  
Translational Inhibition

scholarly journals The pseudophosphatase MK-STYX interacts with G3BP and decreases stress granule formation

2010 ◽  
Vol 427 (3) ◽  
pp. 349-357 ◽  
Author(s):  
Shantá D. Hinton ◽  
Michael P. Myers ◽  
Vincent R. Roggero ◽  
Lizabeth A. Allison ◽  
Nicholas K. Tonks
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Active Form ◽  
Protein Tyrosine Phosphatases ◽  
Stress Granules ◽  
Stress Granule ◽  
Mitogen Activated Protein Kinase ◽  
Granule Formation ◽  
Dual Specificity ◽  
Catalytically Active

MK-STYX [MAPK (mitogen-activated protein kinase) phospho-serine/threonine/tyrosine-binding protein] is a pseudophosphatase member of the dual-specificity phosphatase subfamily of the PTPs (protein tyrosine phosphatases). MK-STYX is catalytically inactive due to the absence of two amino acids from the signature motif that are essential for phosphatase activity. The nucleophilic cysteine residue and the adjacent histidine residue, which are conserved in all active dual-specificity phosphatases, are replaced by serine and phenylalanine residues respectively in MK-STYX. Mutations to introduce histidine and cysteine residues into the active site of MK-STYX generated an active phosphatase. Using MS, we identified G3BP1 [Ras-GAP (GTPase-activating protein) SH3 (Src homology 3) domain-binding protein-1], a regulator of Ras signalling, as a binding partner of MK-STYX. We observed that G3BP1 bound to native MK-STYX; however, binding to the mutant catalytically active form of MK-STYX was dramatically reduced. G3BP1 is also an RNA-binding protein with endoribonuclease activity that is recruited to ‘stress granules’ after stress stimuli. Stress granules are large subcellular structures that serve as sites of mRNA sorting, in which untranslated mRNAs accumulate. We have shown that expression of MK-STYX inhibited stress granule formation induced either by aresenite or expression of G3BP itself; however, the catalytically active mutant MK-STYX was impaired in its ability to inhibit G3BP-induced stress granule assembly. These results reveal a novel facet of the function of a member of the PTP family, illustrating a role for MK-STYX in regulating the ability of G3BP1 to integrate changes in growth-factor stimulation and environmental stress with the regulation of protein synthesis.

scholarly journals LINE-1 ORF1 Protein Localizes in Stress Granules with Other RNA-Binding Proteins, Including Components of RNA Interference RNA-Induced Silencing Complex

2007 ◽  
Vol 27 (18) ◽  
pp. 6469-6483 ◽  
Author(s):  
John L. Goodier ◽  
Lili Zhang ◽  
Melissa R. Vetter ◽  
Haig H. Kazazian
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Protein A ◽  
Rna Binding Protein ◽  
Stress Granules ◽  
Plasminogen Activator Inhibitor ◽  
Cellular Damage ◽  
Activator Inhibitor

ABSTRACT LINE-1 retrotransposons constitute one-fifth of human DNA and have helped shape our genome. A full-length L1 encodes a 40-kDa RNA-binding protein (ORF1p) and a 150-kDa protein (ORF2p) with endonuclease and reverse transcriptase activities. ORF1p is distinctive in forming large cytoplasmic foci, which we identified as cytoplasmic stress granules. A phylogenetically conserved central region of the protein is critical for wild-type localization and retrotransposition. Yeast two-hybrid screens revealed several RNA-binding proteins that coimmunoprecipitate with ORF1p and colocalize with ORF1p in foci. Two of these proteins, YB-1 and hnRNPA1, were previously reported in stress granules. We identified additional proteins associated with stress granules, including DNA-binding protein A, 9G8, and plasminogen activator inhibitor RNA-binding protein 1 (PAI-RBP1). PAI-RBP1 is a homolog of VIG, a part of the Drosophila melanogaster RNA-induced silencing complex (RISC). Other RISC components, including Ago2 and FMRP, also colocalize with PAI-RBP1 and ORF1p. We suggest that targeting ORF1p, and possibly the L1 RNP, to stress granules is a mechanism for controlling retrotransposition and its associated genetic and cellular damage.

scholarly journals The RNA binding protein Musashi1 regulates apoptosis, gene expression and stress granule formation in urothelial carcinoma cells

2010 ◽  
Vol 15 (5) ◽  
pp. 1210-1224 ◽  
Author(s):  
Parvaneh Nikpour ◽  
Modjtaba Emadi Baygi ◽  
Christine Steinhoff ◽  
Christiane Hader ◽  
Anna C. Luca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Urothelial Carcinoma ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Carcinoma Cells ◽  
Stress Granule ◽  
Granule Formation ◽  
Apoptosis Gene

scholarly journals Chicken RNA-binding protein T-cell internal antigen-1 contributes to stress granule formation in chicken cells and tissues

2018 ◽  
Vol 19 (1) ◽  
pp. 3
Author(s):  
Yingjie Sun ◽  
Pin Zhang ◽  
Hang Zheng ◽  
Luna Dong ◽  
Lei Tan ◽  
...  
Keyword(s):  
T Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granule ◽  
Granule Formation

scholarly journals Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP

2008 ◽  
Vol 181 (4) ◽  
pp. 639-653 ◽  
Author(s):  
Hironori Kawahara ◽  
Takao Imai ◽  
Hiroaki Imataka ◽  
Masafumi Tsujimoto ◽  
Ken Matsumoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Translation Initiation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granules ◽  
Translational Repression ◽  
Rna Recognition Motifs ◽  
Recognition Motifs

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem cells. We previously reported that Msi1 contributes to the maintenance of the immature state and self-renewal activity of neural stem cells through translational repression of m-Numb. However, its translation repression mechanism has remained unclear. Here, we identify poly(A) binding protein (PABP) as an Msi1-binding protein, and find Msi1 competes with eIF4G for PABP binding. This competition inhibits translation initiation of Msi1's target mRNA. Indeed, deletion of the PABP-interacting domain in Msi1 abolishes its function. We demonstrate that Msi1 inhibits the assembly of the 80S, but not the 48S, ribosome complex. Consistent with these conclusions, Msi1 colocalizes with PABP and is recruited into stress granules, which contain the stalled preinitiation complex. However, Msi1 with mutations in two RNA recognition motifs fails to accumulate into stress granules. These results provide insight into the mechanism by which sequence-specific translational repression occurs in stem cells through the control of translation initiation.

scholarly journals Whi3, an S. cerevisiae RNA-Binding Protein, Is a Component of Stress Granules That Regulates Levels of Its Target mRNAs

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84060 ◽  
Author(s):  
Kristen J. Holmes ◽  
Daniel M. Klass ◽  
Evan L. Guiney ◽  
Martha S. Cyert
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granules ◽  
Target Mrnas

scholarly journals The QKI-6 RNA Binding Protein Localizes with the MBP mRNAs in Stress Granules of Glial Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12824 ◽  
Author(s):  
Yunling Wang ◽  
Geneviève Lacroix ◽  
Jeffery Haines ◽  
Evgueni Doukhanine ◽  
Guillermina Almazan ◽  
...  
Keyword(s):  
Glial Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granules

scholarly journals Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 395 ◽  
Author(s):  
Matthias Kübler ◽  
Sebastian Beck ◽  
Silvia Fischer ◽  
Philipp Götz ◽  
Konda Kumaraswami ◽  
...  
Keyword(s):  
Muscle Tissue ◽  
Rna Binding ◽  
Binding Protein ◽  
Macrophage Polarization ◽  
Rna Binding Protein ◽  
Total Leukocyte Count ◽  
Sham Operation ◽  
Ischemic Tissue ◽  
Ischemic Muscle ◽  
Deficient Mice

Cold-inducible RNA-binding protein (CIRP) is an intracellular RNA-chaperone and extracellular promoter of inflammation, which is increasingly expressed and released under conditions of hypoxia and cold stress. The functional relevance of CIRP for angiogenesis and regeneration of ischemic muscle tissue has never been investigated and is the topic of the present study. We investigated the role of CIRP employing CIRP deficient mice along with a hindlimb model of ischemia-induced angiogenesis. 1 and 7 days after femoral artery ligation or sham operation, gastrocnemius muscles of CIRP-deficient and wildtype mice were isolated and processed for (immuno-) histological analyses. CIRP deficient mice showed decreased ischemic tissue damage as evidenced by Hematoxylin and Eosin staining, whereas angiogenesis was enhanced as demonstrated by increased capillary/muscle fiber ratio and number of proliferating endothelial (CD31+/BrdU+) cells on day 7 after surgery. Moreover, CIRP deficiency resulted in a reduction of total leukocyte count (CD45+), neutrophils (myeloperoxidase, MPO+), neutrophil extracellular traps (NETs) (MPO+/CitH3+), and inflammatory M1-like polarized macrophages (CD68+/MRC1-), whereas the number of tissue regenerating M2-like polarized macrophages (CD68+/MRC1-) was increased in ischemic tissue samples. In summary, we show that the absence of CIRP ameliorates angiogenesis and regeneration of ischemic muscle tissue, most likely by influencing macrophage polarization in direction to regenerative M2-like macrophages.

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