scholarly journals The RNA-binding protein HuR regulates intestinal epithelial restitution by modulating Caveolin-1 gene expression

2020 ◽  
Author(s):  
Shan Cao ◽  
Lan Xiao ◽  
Junyao Wang ◽  
Guodong Chen ◽  
Yulan Liu
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Mrna Levels ◽  
Epithelial Repair ◽  
Caveolin 1 ◽  
Protein Levels ◽  
Ectopic Overexpression

The integrity of the intestinal mucosal barrier protects hosts against pathological conditions. Early mucosal restitution after wounding refers to epithelial cell migration into a defect. The RNA-binding protein HuR plays an important role in the posttranscriptional regulation of gene expression and is involved in many aspects of cellular physiology. In the present study, we investigated the role of HuR in the regulation of cell migration through the posttranscriptional regulation of Caveolin-1 (Cav-1). Online software was used to identify Cav-1 mRNA as a potential target of HuR. The interaction of HuR with Cav-1 mRNA was investigated via ribonucleoprotein immunoprecipitation (RNP IP) assays and biotin pulldown analysis. HuR was found to bind specifically to the Cav-1 3’-UTR rather than the coding region or 5’-UTR. Transfection of cells with siHuR decreased both HuR protein levels and Cav-1 protein levels; conversely, ectopic overexpression of HuR via infection of cells with an adenoviral vector containing HuR cDNA (AdHuR) increased Cav-1 protein levels without disturbing Cav-1 mRNA levels. Thus, HuR enhanced Cav-1 expression in vitro by stimulating Cav-1 translation. Intestinal epithelium–specific HuR knockout in mice decreased Cav-1 protein levels without changing Cav-1 mRNA levels, consistent with the in vitro results. Decreasing the levels of HuR via siHuR transfection inhibited early epithelial repair, but this effect was reversed by ectopic overexpression of GFP-tagged Cav-1. These results indicate that posttranscriptional regulation of Cav-1 gene expression by HuR plays a critical role in the regulation of rapid epithelial repair after wounding.

scholarly journals Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP 1/ IGF 2 BP 1

EMBO Reports ◽  
2019 ◽  
Vol 20 (6) ◽  
Author(s):  
Priya Chatterji ◽  
Patrick A Williams ◽  
Kelly A Whelan ◽  
Fernando C Samper ◽  
Sarah F Andres ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Repair

Cold-induced RNA-binding protein (CIRBP) regulates the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) during heat stress-induced testicular injury

2020 ◽  
Vol 32 (18) ◽  
pp. 1357
Author(s):  
Chengcheng Xu ◽  
Dandan Ke ◽  
Liping Zou ◽  
Nianyu Li ◽  
Yingying Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Protein Expression ◽  
Rna Binding ◽  
Cell Model ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Testicular Injury

In this study, the ability of cold-induced RNA-binding protein (CIRBP) to regulate the expression of Src-associated during mitosis of 68 kDa (Sam68) and extracellular signal-regulated kinases (ERK) in the mouse testis and mouse primary spermatocytes (GC-2spd cell line) before and after heat stress was examined to explore the molecular mechanism by which CIRBP decreases testicular injury. A mouse testicular hyperthermia model, a mouse primary spermatocyte hyperthermia model and a low CIRBP gene-expression cell model were constructed and their relevant parameters were analysed. The mRNA and protein levels of CIRBP and Sam68 were significantly decreased in the 3-h and 12-h testicular heat-stress groups, extracellular signal-regulated kinase 1/2 (ERK1/2) protein expression was not significantly affected but phospho-ERK1/2 protein levels were significantly decreased. GC-2spd cellular heat-stress results showed that the mRNA and protein concentrations of CIRBP and Sam68 were reduced 48h after heat stress. In the low CIRBP gene-expression cell model, CIRBP protein expression was significantly decreased. Sam68 mRNA expression was significantly decreased only at the maximum transfection concentration of 50nM and Sam68 protein expression was not significantly affected. These findings suggest that CIRBP may regulate the expression of Sam68 at the transcriptional level and the expression of phospho-ERK1/2 protein, both of which protect against heat-stress-induced testicular injury in mice.

scholarly journals The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis

Leukemia ◽  
2021 ◽  
Author(s):  
Tiffany M. Tran ◽  
Julia Philipp ◽  
Jaspal Singh Bassi ◽  
Neha Nibber ◽  
Jolene M. Draper ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Leukemia Cell ◽  
Cellular Level ◽  
Ras Signaling ◽  
Mrna Levels ◽  
Minimal Impact ◽  
Poor Outcomes

AbstractDespite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.

scholarly journals Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1

EMBO Reports ◽  
2021 ◽  
Author(s):  
Priya Chatterji ◽  
Patrick A Williams ◽  
Kelly A Whelan ◽  
Fernando C Samper ◽  
Sarah F Andres ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Repair

scholarly journals A Putative RNA-Binding Protein Positively Regulates Salicylic Acid–Mediated Immunity in Arabidopsis

2010 ◽  
Vol 23 (12) ◽  
pp. 1573-1583 ◽  
Author(s):  
Yiping Qi ◽  
Kenichi Tsuda ◽  
Anna Joe ◽  
Masanao Sato ◽  
Le V. Nguyen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salicylic Acid ◽  
Pseudomonas Syringae ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Tomato Dc3000 ◽  
Overexpression Line

RNA-binding proteins (RBP) can control gene expression at both transcriptional and post-transcriptional levels. Plants respond to pathogen infection with rapid reprogramming of gene expression. However, little is known about how plant RBP function in plant immunity. Here, we describe the involvement of an RBP, Arabidopsis thaliana RNA-binding protein-defense related 1 (AtRBP-DR1; At4g03110), in resistance to the pathogen Pseudomonas syringae pv. tomato DC3000. AtRBP-DR1 loss-of-function mutants showed enhanced susceptibility to P. syringae pv. tomato DC3000. Overexpression of AtRBP-DR1 led to enhanced resistance to P. syringae pv. tomato DC3000 strains and dwarfism. The hypersensitive response triggered by P. syringae pv. tomato DC3000 avrRpt2 was compromised in the Atrbp-dr1 mutant and enhanced in the AtRBP-DR1 overexpression line at early time points. AtRBP-DR1 overexpression lines showed higher mRNA levels of SID2 and PR1, which are salicylic acid (SA) inducible, as well as spontaneous cell death in mature leaves. Consistent with these observations, the SA level was low in the Atrbp-dr1 mutant but high in the overexpression line. The SA-related phenotype in the overexpression line was fully dependent on SID2. Thus, AtRBP-DR1 is a positive regulator of SA-mediated immunity, possibly acting on SA signaling-related genes at a post-transcriptional level.

scholarly journals Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16

2003 ◽  
Vol 30 (2) ◽  
pp. 253-262 ◽  
Author(s):  
M Imae ◽  
Z Fu ◽  
A Yoshida ◽  
T Noguchi ◽  
H Kato
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Fold Increase ◽  
Mrna Levels ◽  
Hormonal Factors ◽  
Protein Levels ◽  
Nuclear Exclusion ◽  
Protein Free Diet

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.

scholarly journals The RNA-Binding Protein ELAVL1 Regulates GnRH Receptor Expression and the Response to GnRH

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1999-2014 ◽  
Author(s):  
Tomohiro Terasaka ◽  
Taeshin Kim ◽  
Hiral Dave ◽  
Bhakti Gangapurkar ◽  
Dequina A Nicholas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Gnrh Receptor ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Mrna Levels ◽  
Lh Secretion ◽  
Stimulation Of

Abstract Gonadotropin secretion, which is elicited by GnRH stimulation of the anterior pituitary gonadotropes, is a critical feature of reproductive control and the maintenance of fertility. In addition, activation of the GnRH receptor (GnRHR) regulates transcription and translation of multiple factors that regulate the signaling response and synthesis of gonadotropins. GnRH stimulation results in a broad redistribution of mRNA between active and inactive polyribosomes within the cell, but the mechanism of redistribution is not known. The RNA-binding protein embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) binds to AU-rich elements in mRNA and is one of the most abundant mRNA-binding proteins in eukaryotic cells. It is known to serve as a core component of RNA-binding complexes that direct the fate of mRNA. In LβT2 gonadotropes, we showed that ELAVL1 binds to multiple mRNAs encoding factors that are crucial for gonadotropin synthesis and release. Association with some mRNAs is GnRH sensitive but does not correlate with abundance of binding. We also showed MAPK-dependent changes in intracellular localization of ELAVL1 in response to GnRH stimulation. Knockdown of ELAVL1 gene expression resulted in reduced Lhb and Gnrhr mRNA levels, reduced cell surface expression of GnRHR, and reduced LH secretion in response to GnRH stimulation. Overall, these observations not only support the role of ELAVL1 in GnRHR-mediated regulation of gene expression and LH secretion but also indicate that other factors may contribute to the precise fate of mRNA in response to GnRH stimulation of gonadotropes.

scholarly journals The RNA-Binding Protein PCBP1 Functions as a Tumor Suppressor in Prostate Cancer by Inhibiting Mitogen Activated Protein Kinase 1

2018 ◽  
Vol 48 (4) ◽  
pp. 1747-1754 ◽  
Author(s):  
Yingying Zhang ◽  
Lin Meng ◽  
Lin Xiao ◽  
Ruiwang Liu ◽  
Zhonghai Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Mitogen Activated Protein

Background/Aims: Poly r(C) binding protein (PCBP) 1 or heterogeneous ribonucleoprotein (hnRNP) E1 is a RNA binding protein functional in multiple biological processes. In prostate cancer (PCa), PCBP1 loss was shown to be involved with increased stemness in PCacells; however, the underlying mechanism remains unclear. Method: The role of PCBP1 in prostate tumor formationwas determined by xenograft assays. Immunoprecipitationand mass spectrometry were performed to find the pathways altered after PCBP1 knockdown. Cell proliferation, migration, invasion, and soft agar colony formationassays and xenograft assays were used to determine the role of target protein pathogenesis regulation and formation of PCa. QRT-PCR was performedto quantify relative mRNA expression. Results: The expression of mitogen activated protein kinase 1 (MAPK1) or extracellular signal regulated kinase 2 (ERK2) was increased following PCBP1 loss. Attenuation of MAPK1 inhibited in vitro and in vivo tumorigenicity and metastasis in PCa cell line, PC3. Overexpression of MAPK1 in the PC3 cells increased the tumorigenicity and metastasis. Analysis of PCBP1 and MAPK1 mRNA levels in 25 PCa patients compared to tumor-adjacent normal tissue confirmed an inverse correlation between PCBP1 and MAPK1 expression. Conclusions: PCBP1 can act as a suppressor of tumor in prostate epithelial cells by inhibiting MAPK1 expression.

scholarly journals Ontogeny of malate-aspartate shuttle capacity and gene expression in cardiac mitochondria

1998 ◽  
Vol 274 (3) ◽  
pp. C780-C788 ◽  
Author(s):  
Thomas D. Scholz ◽  
Stacia L. Koppenhafer ◽  
Cynthia J. Teneyck ◽  
Brian C. Schutte
Keyword(s):  
Gene Expression ◽  
Malate Dehydrogenase ◽  
Posttranscriptional Regulation ◽  
Time Course ◽  
Cardiac Tissue ◽  
Mrna Levels ◽  
Cardiac Mitochondria ◽  
Protein Levels ◽  
Mitochondrial Malate Dehydrogenase ◽  
Malate Aspartate Shuttle

Developmental downregulation of the malate-aspartate shuttle has been observed in cardiac mitochondria. The goals of this study were to determine the time course of the postnatal decline and to identify potential regulatory sites by measuring steady-state myocardial mRNA and protein levels of the mitochondrial proteins involved in the shuttle. By use of isolated porcine cardiac mitochondria incubated with saturating concentrations of the cytosolic components of the malate-aspartate shuttle, shuttle capacity was found to decline by ∼50% during the first 5 wk of life (from 921 ± 48 to 531 ± 53 nmol ⋅ min−1 ⋅ mg protein−1). Mitochondrial aspartate aminotransferase mRNA levels were greater in adult than in newborn myocardium. mRNA levels of mitochondrial malate dehydrogenase in adult cardiac tissue were 224% of levels in newborn tissue, whereas protein levels were 54% greater in adult myocardium. Aspartate/glutamate carrier protein levels were also greater in adult than in newborn tissue. mRNA and protein levels of the oxoglutarate/malate carrier were increased in newborn myocardium. It was concluded that 1) myocardial malate-aspartate shuttle capacity declines rapidly after birth, 2) divergence of mitochondrial malate dehydrogenase mRNA and protein levels during development suggests posttranscriptional regulation of this protein, and 3) the developmental decline in malate-aspartate shuttle capacity is regulated by decreased oxoglutarate/malate carrier gene expression.

Deleted in breast cancer 1 plays a functional role in adipocyte differentiation

2015 ◽  
Vol 308 (7) ◽  
pp. E554-E561 ◽  
Author(s):  
José María Moreno-Navarrete ◽  
María Moreno ◽  
Marta Vidal ◽  
Francisco Ortega ◽  
Marta Serrano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Wide Spectrum ◽  
Human Adipose Tissue ◽  
Mrna Levels ◽  
Negatively Associated ◽  
Adipoq Gene ◽  
Protein Levels

Genetic deletion of Dbc1 in mice reduced adipose tissue senescence and inflammation while promoting an expansion of this tissue. Here, we aimed to investigate DBC1 mRNA and protein levels in human adipose tissue from subjects with a wide spectrum of fat mass ( cohort 1; n = 105) and insulin resistance ( cohort 2; n = 47); we also investigated the effects of DBC1 knockdown on 3T3-L1 adipocyte differentiation. DBC1 mRNA was relatively abundant in both visceral (VAT) and subcutaneous adipose tissue (SAT) (mainly in the adipocyte fraction), being decreased in adipose tissue from obese compared with lean subjects. In both VAT and SAT, DBC1 mRNA levels were negatively associated with BMI and positively associated with age and the expression of PPARγ, GLUT4, IRS1, lipogenic ( FASN, ACACA), lipid droplet-associated genes ( PLIN1, FSP27, ADRP, and TIP47), and lipolytic ( ABDH5, AKAP, and PRKACA) genes but negatively associated with ADIPOQ in VAT. DBC1 mRNA and protein levels were increased in the early stages of adipocyte differentiation of human and 3T3-L1 adipocytes. Dbc1 knockdown (KD) with lentivirus led to enhanced adipocyte differentiation, increasing intracellular lipid accumulation and adipogenic gene expression. In conclusion, although DBC1 gene expression was reduced in adipose tissue from obese subjects, it was negatively associated with ADIPOQ gene expression in VAT, suggesting that DBC1 might promote visceral adipose tissue dysfunction. In vitro data supported the antiadipogenic effects of DBC1.

Sign in / Sign up

Export Citation Format

Share Document