scholarly journals Dynamic regulation of immunity through post-translational control of defense transcript splicing

2019 ◽  
Author(s):  
Keini Dressano ◽  
Philipp R Weckwerth ◽  
Elly Poretsky ◽  
Yohei Takahashi ◽  
Carleen Villarreal ◽  
...  
Keyword(s):  
Immune Responses ◽  
Translational Control ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Negative Regulator ◽  
Signaling Proteins ◽  
Receptor Signaling ◽  
Post Translational Modification ◽  
Defense Signaling

AbstractSurvival of all living organisms requires the ability to detect attack and swiftly counter with protective immune responses. Despite considerable mechanistic advances, interconnectivity of signaling circuits often remains unclear. A newly-characterized protein, IMMUNOREGULATORY RNA-BINDING PROTEIN (IRR), negatively regulates immune responses in both maize and Arabidopsis, with disrupted function resulting in enhanced disease resistance. IRR physically interacts with, and promotes canonical splicing of, transcripts encoding defense signaling proteins, including the key negative regulator of pattern recognition receptor signaling complexes, CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28). Upon immune activation by Plant Elicitor Peptides (Peps), IRR is dephosphorylated, disrupting interaction withCPK28transcripts and resulting in accumulation of an alternative splice variant encoding a truncated CPK28 protein with impaired kinase activity and diminished function as a negative regulator. We demonstrate a novel circuit linking Pep-induced post-translational modification of IRR with post-transcriptionally-mediated attenuation of CPK28 function to dynamically amplify Pep signaling and immune output.One Sentence SummaryPlant innate immunity is promoted by post-translational modification of a novel RNA-binding protein that regulates alternative splicing of transcripts encoding defense signaling proteins to dynamically increase immune receptor signaling capacity through deactivation of a key signal-buffering circuit.

scholarly journals The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4+ T Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Rudolf Käfer ◽  
Lisa Schmidtke ◽  
Katharina Schrick ◽  
Evelyn Montermann ◽  
Matthias Bros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Control Group ◽  
Type I

The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP-/-) interferes with T cell activation and polarization. Polyclonally stimulated KSRP-/- CD4+ T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP-/- CD4+ T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP-/- CD8+ T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon-γ. Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP-/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3′ untranslated region of IL-13, IL-10, and IFN-γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP-/- CD4+ T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP-/- CD4+ T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP-/- mice favor Th2-driven immune responses.

scholarly journals Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis

2016 ◽  
Vol 27 (15) ◽  
pp. 2341-2350 ◽  
Author(s):  
Patrick A. Williams ◽  
Michael S. Krug ◽  
Emily A. McMillan ◽  
Jasmine D. Peake ◽  
Tara L. Davis ◽  
...  
Keyword(s):  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Negative Regulator ◽  
Transgenic Expression ◽  
Male Germline ◽  
Deleted In Azoospermia

Developing male germ cells are exquisitely sensitive to environmental insults such as heat and oxidative stress. An additional characteristic of these cells is their unique dependence on RNA-binding proteins for regulating posttranscriptional gene expression and translational control. Here we provide a mechanistic link unifying these two features. We show that the germ cell–specific RNA-binding protein deleted in azoospermia-like (Dazl) is phosphorylated by MAPKAP kinase 2 (MK2), a stress-induced protein kinase activated downstream of p38 MAPK. We demonstrate that phosphorylation of Dazl by MK2 on an evolutionarily conserved serine residue inhibits its interaction with poly(A)-binding protein, resulting in reduced translation of Dazl-regulated target RNAs. We further show that transgenic expression of wild-type human Dazl but not a phosphomimetic form in the Drosophila male germline can restore fertility to flies deficient in boule, the Drosophila orthologue of human Dazl. These results illuminate a novel role for MK2 in spermatogenesis, expand the repertoire of RNA-binding proteins phosphorylated by this kinase, and suggest that signaling by the p38-MK2 pathway is a negative regulator of spermatogenesis via phosphorylation of Dazl.

scholarly journals The Nuclear RNA-binding Protein Sam68 Translocates to the Cytoplasm and Associates with the Polysomes in Mouse Spermatocytes

2006 ◽  
Vol 17 (1) ◽  
pp. 14-24 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Francesca Zalfa ◽  
Flavia Botti ◽  
Raffaele Geremia ◽  
Claudia Bagni ◽  
...  
Keyword(s):  
Translational Control ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Male Meiosis ◽  
Binding Motif ◽  
Mitogen Activated Protein ◽  
Pachytene Spermatocytes ◽  
And Function

Translational control plays a crucial role during gametogenesis in organisms as different as worms and mammals. Mouse knockout models have highlighted the essential function of many RNA-binding proteins during spermatogenesis. Herein we have investigated the expression and function during mammalian male meiosis of Sam68, an RNA-binding protein implicated in several aspects of RNA metabolism. Sam68 expression and localization within the cells is stage specific: it is expressed in the nucleus of spermatogonia, it disappears at the onset of meiosis (leptotene/zygotene stages), and it accumulates again in the nucleus of pachytene spermatocytes and round spermatids. During the meiotic divisions, Sam68 translocates to the cytoplasm where it is found associated with the polysomes. Translocation correlates with serine/threonine phosphorylation and it is blocked by inhibitors of the mitogen activated protein kinases ERK1/2 and of the maturation promoting factor cyclinB-cdc2 complex. Both kinases associate with Sam68 in pachytene spermatocytes and phosphorylate the regulatory regions upstream and downstream of the Sam68 RNA-binding motif. Molecular cloning of the mRNAs associated with Sam68 in mouse spermatocytes reveals a subset of genes that might be posttranscriptionally regulated by this RNA-binding protein during spermatogenesis. We also demonstrate that Sam68 shuttles between the nucleus and the cytoplasm in secondary spermatocytes, suggesting that it may promote translation of specific RNA targets during the meiotic divisions.

scholarly journals Spnr, a murine RNA-binding protein that is localized to cytoplasmic microtubules.

1995 ◽  
Vol 129 (4) ◽  
pp. 1023-1032 ◽  
Author(s):  
J M Schumacher ◽  
K Lee ◽  
S Edelhoff ◽  
R E Braun
Keyword(s):  
Translational Control ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Translational Repression ◽  
Rna Transport ◽  
Binding Domains ◽  
Cytoplasmic Microtubules ◽  
Pachytene Spermatocytes ◽  
Expression Libraries

Previous studies in transgenic mice have established the importance of the 3' untranslated region (UTR) of the spermatid-specific protamine-1 (Prm-1) mRNA in its translational control during male germ cell development. To clone genes that mediate the translational repression or activation of the Prm-1 mRNA, we screened cDNA expression libraries made with RNA from pachytene spermatocytes and round spermatids, with an RNA probe corresponding to the 3' UTR of Prm-1. We obtained six independent clones that encode Spnr, a spermatid perinuclear RNA-binding protein. Spnr is a 71-kD protein that contains two previously described RNA binding domains. The Spnr mRNA is expressed at high levels in the testis, ovary, and brain, and is present in multiple forms in those tissues. Immunolocalization of the Spnr protein within the testis shows that it is expressed exclusively in postmeiotic germ cells and that it is localized to the manchette, a spermatid-specific microtubular array. Although the Spnr protein is expressed too late to be directly involved in the translational repression of Prm-1 specifically, we suggest that the Spnr protein may be involved in other aspects of spermatid RNA metabolism, such as RNA transport or translational activation.

scholarly journals Cbk1 Regulation of the RNA-Binding Protein Ssd1 Integrates Cell Fate with Translational Control

2009 ◽  
Vol 19 (24) ◽  
pp. 2114-2120 ◽  
Author(s):  
Jaclyn M. Jansen ◽  
Antony G. Wanless ◽  
Christopher W. Seidel ◽  
Eric L. Weiss
Keyword(s):  
Cell Fate ◽  
Translational Control ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Xenopus laevis zygote arrest 2 (zar2) encodes a zinc finger RNA-binding protein that binds to the translational control sequence in the maternal Wee1 mRNA and regulates translation

2012 ◽  
Vol 369 (2) ◽  
pp. 177-190 ◽  
Author(s):  
Amanda Charlesworth ◽  
Tomomi M. Yamamoto ◽  
Jonathan M. Cook ◽  
Kevin D. Silva ◽  
Cassandra V. Kotter ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Zinc Finger ◽  
Translational Control ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Control Sequence

scholarly journals The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming

Development ◽  
2019 ◽  
Vol 146 (19) ◽  
pp. dev175950 ◽  
Author(s):  
Victor A. Ruthig ◽  
Matthew B. Friedersdorf ◽  
Jason A. Garness ◽  
Steve C. Munger ◽  
Corey Bunce ◽  
...  
Keyword(s):  
Germ Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Negative Regulator ◽  
Cell Reprogramming ◽  
Positive Regulator ◽  
Epigenetic Modifiers
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