scholarly journals Targeted Knockdown of RNA-Binding Protein TIAR for Promoting Self-Renewal and Attenuating Differentiation of Mouse Embryonic Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Zhe Geng ◽  
Ping Li ◽  
Li Tan ◽  
Houyan Song

RNA-binding protein TIAR has been suggested to mediate the translational silencing of ARE-containing mRNAs. To analyze the functions of TIAR, we established RNAi and genetic rescue assays. We evaluated the expression of neuroectoderm markers Pax6 and nestin, mesoderm markers brachyury and Flk1, and hypoblast and definitive endoderm markers Sox17 and Gata6 during EB differentiation and found that knockdown TIAR expression restrained the differentiation of E14 cells. We assessed gene expression levels of Flk-1 and VE-cadherin and observed attenuated differentiation of E14 cells into endothelial cells upon downregulation of TIAR gene expression. As such, we hypothesized an essential role of TIAR related to EB differentiation. As TIAR inhibits the translation of c-myc, we proposed that downregulation of TIAR results in restrained differentiation of E14 cells, due in part to the function of c-myc. We found that TIAR inhibited c-myc expression at the translational level in E14 cells; accordingly, a reduction of TIAR expression promoted self-renewal of pluripotent cells and attenuated differentiation. Additionally, we established that TIAR inhibited TIA-1 expression at the translational level in E14 cells. Taken together, we have contributed to the understanding of the regulatory relationships between TIAR and both c-myc and TIA-1.

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.


Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 361
Author(s):  
Myeongwoo Jung ◽  
Eun-Kyung Lee

HuD (also known as ELAVL4) is an RNA–binding protein belonging to the human antigen (Hu) family that regulates stability, translation, splicing, and adenylation of target mRNAs. Unlike ubiquitously distributed HuR, HuD is only expressed in certain types of tissues, mainly in neuronal systems. Numerous studies have shown that HuD plays essential roles in neuronal development, differentiation, neurogenesis, dendritic maturation, neural plasticity, and synaptic transmission by regulating the metabolism of target mRNAs. However, growing evidence suggests that HuD also functions as a pivotal regulator of gene expression in non–neuronal systems and its malfunction is implicated in disease pathogenesis. Comprehensive knowledge of HuD expression, abundance, molecular targets, and regulatory mechanisms will broaden our understanding of its role as a versatile regulator of gene expression, thus enabling novel treatments for diseases with aberrant HuD expression. This review focuses on recent advances investigating the emerging role of HuD, its molecular mechanisms of target gene regulation, and its disease relevance in both neuronal and non–neuronal systems.


Cell Reports ◽  
2021 ◽  
Vol 35 (9) ◽  
pp. 109198
Author(s):  
Shlomi Dvir ◽  
Amir Argoetti ◽  
Chen Lesnik ◽  
Mark Roytblat ◽  
Kohava Shriki ◽  
...  

FEBS Open Bio ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1964-1976 ◽  
Author(s):  
Nirmala Tilija Pun ◽  
Amrita Khakurel ◽  
Aastha Shrestha ◽  
Sang‐Hyun Kim ◽  
Pil‐Hoon Park

2018 ◽  
Vol 154 (6) ◽  
pp. S-585
Author(s):  
Sarah F. Andres ◽  
Kathy N. Williams ◽  
Kathryn E. Hamilton ◽  
Rei Mizuno ◽  
Jeff Headd ◽  
...  

2016 ◽  
Vol 44 (5) ◽  
pp. 1321-1337 ◽  
Author(s):  
Andrew R. Clark ◽  
Jonathan L.E. Dean

Twenty years ago, the first description of a tristetraprolin (TTP) knockout mouse highlighted the fundamental role of TTP in the restraint of inflammation. Since then, work from several groups has generated a detailed picture of the expression and function of TTP. It is a sequence-specific RNA-binding protein that orchestrates the deadenylation and degradation of several mRNAs encoding inflammatory mediators. It is very extensively post-translationally modified, with more than 30 phosphorylations that are supported by at least two independent lines of evidence. The phosphorylation of two particular residues, serines 52 and 178 of mouse TTP (serines 60 and 186 of the human orthologue), has profound effects on the expression, function and localisation of TTP. Here, we discuss the control of TTP biology via its phosphorylation and dephosphorylation, with a particular focus on recent advances and on questions that remain unanswered.


2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Weibin Zha ◽  
Guangji Wang ◽  
Beth S. Pecora ◽  
Elaine Studer ◽  
Phillip B Hylemon ◽  
...  

2010 ◽  
Vol 222 (3) ◽  
pp. 223-226 ◽  
Author(s):  
David J Elliott ◽  
Prabhakar Rajan

Sign in / Sign up

Export Citation Format

Share Document