scholarly journals RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism

2017 ◽  
Vol 127 (10) ◽  
pp. 3741-3754 ◽  
Author(s):  
Elizabeth J. Tarling ◽  
Bethan L. Clifford ◽  
Joan Cheng ◽  
Pauline Morand ◽  
Angela Cheng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Posttranscriptional Regulation ◽  
Acid Metabolism ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Bile Acid Metabolism

Abstract 402: Post-transcriptional Regulation of Bile Acid Metabolism by the RNA binding protein ZFP36L1

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Elizabeth Tarling ◽  
Joan Cheng ◽  
Angela Cheng ◽  
Pauline Morand ◽  
Bethan Clifford ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Rna Binding ◽  
Binding Protein ◽  
Plasma Cholesterol ◽  
Rna Binding Protein ◽  
Lipid Absorption ◽  
Bile Acid Metabolism ◽  
Mrna Levels

Bile acids are detergents and important signaling molecules that activate the nuclear receptor FXR to control key metabolic processes, including feedback mechanisms to maintain bile acid homeostasis. Activation of FXR decreases the mRNA levels of several bile acid synthetic genes, including the rate-limiting enzyme Cyp7a1 . Here we show that Cyp7a1 mRNA levels are very rapidly reduced following FXR activation, indicative of a post-transcriptional mechanism. We identify the RNA binding protein Zfp36l1 as an FXR target gene and show that hepatic overexpression of ZFP36L1 in mice decreases Cyp7a1 mRNA levels. In contrast, Zfp36l1 L -KO mice have increased levels of Cyp7a1 mRNA and biliary bile acids as well as reduced plasma cholesterol levels. Zfp36l1 L -KO mice fed a Western diet have reduced diet-induced obesity and steatosis, likely due to impaired lipid absorption, consistent with increased Cyp7a1 levels. Thus, the ZFP36L1-dependent regulation of bile acid metabolism is an important metabolic contributor of dyslipidemia, obesity and hepatosteatosis.

scholarly journals The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

2011 ◽  
Vol 22 (16) ◽  
pp. 2875-2885 ◽  
Author(s):  
Mai Nguyen Chi ◽  
Jacques Auriol ◽  
Bernard Jégou ◽  
Dimitris L. Kontoyiannis ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Germ Cells ◽  
Posttranscriptional Regulation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Female Sterility ◽  
Targeted Deletion

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.

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

Role of the RNA-binding protein HuR in posttranscriptional regulation of IL-13 in T cells

2007 ◽  
Vol &NA; ◽  
pp. S35
Author(s):  
Cristiana Stellato ◽  
J Fang ◽  
B Tancowny ◽  
J Fan ◽  
F Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals RNA-Binding Protein HuR Is Required for Stabilization of SLC11A1 mRNA and SLC11A1 Protein Expression

2005 ◽  
Vol 25 (18) ◽  
pp. 8139-8149 ◽  
Author(s):  
Yong Zhong Xu ◽  
Sergio Di Marco ◽  
Imed Gallouzi ◽  
Marek Rola-Pleszczynski ◽  
Danuta Radzioch
Keyword(s):  
Posttranscriptional Regulation ◽  
Macrophage Activation ◽  
Rna Binding ◽  
Binding Protein ◽  
Mrna Level ◽  
Rna Binding Protein ◽  
Cytoplasmic Localization ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Solute Carrier

ABSTRACT The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene is associated with infectious and autoimmune diseases and plays an important role in macrophage activation. Human SLC11A1 mRNA contains an AU-rich element (ARE) within the 3′ untranslated region; however, its role in the regulation of SLC11A1 gene expression has not been elucidated. Here we analyze the expression of SLC11A1 in human monocytes and HL-60 cells and then use HL-60 cells as a model to determine whether RNA-binding protein HuR is associated with the ARE and involved in SLC11A1 mRNA turnover. Our results demonstrate a binding of HuR to the SLC11A1 ARE in phorbol myristate acetate (PMA)-differentiated cells dramatically increased compared to that in undifferentiated cells. Interestingly, PMA-induced accumulation of cytoplasmic HuR occurs in parallel with an increase in the binding of HuR to SLC11A1 ARE and with an increase in the SLC11A1 mRNA level. This suggests that HuR's cytoplasmic localization plays an important role in the regulation of SLC11A1 expression. We also observe that down-regulation of HuR expression by RNA interference (RNAi) results in a decrease in SLC11A1 expression which can be restored by the addition of recombinant HuR protein to the RNAi-treated cells. Finally, we show that HuR overexpression in HL-60 cells significantly increases the SLC11A1 mRNA stability. Taken together, our data demonstrate that HuR is a key mediator of posttranscriptional regulation and expression of the SLC11A1 gene.

Role of the RNA-binding Protein HuR in Posttranscriptional Regulation of IL-13 in T Cells

2007 ◽  
Vol 119 (1) ◽  
pp. S133
Author(s):  
C. Stellato ◽  
X. Fang ◽  
B. Tancowny ◽  
J. Fan ◽  
F. Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Hepatic deletion of X-box binding protein 1 impairs bile acid metabolism in mice

2016 ◽  
Vol 58 (3) ◽  
pp. 504-511 ◽  
Author(s):  
Xiaoying Liu ◽  
Anne S. Henkel ◽  
Brian E. LeCuyer ◽  
Susan C. Hubchak ◽  
Matthew J. Schipma ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Bile Acid Metabolism

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.

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