Faculty Opinions recommendation of Nuclear import of cytoplasmic poly(A) binding protein restricts gene expression via hyperadenylation and nuclear retention of mRNA.

Author(s):  
Megerditch Kiledjian
Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 104 ◽  
Author(s):  
Dmitry A. Kretov ◽  
Daria A. Mordovkina ◽  
Irina A. Eliseeva ◽  
Dmitry N. Lyabin ◽  
Dmitry N. Polyakov ◽  
...  

The Y-box binding protein 1 (YB-1) is an RNA/DNA-binding protein regulating gene expression in the cytoplasm and the nucleus. Although mostly cytoplasmic, YB-1 accumulates in the nucleus under stress conditions. Its nuclear localization is associated with aggressiveness and multidrug resistance of cancer cells, which makes the understanding of the regulatory mechanisms of YB-1 subcellular distribution essential. Here, we report that inhibition of RNA polymerase II (RNAPII) activity results in the nuclear accumulation of YB-1 accompanied by its phosphorylation at Ser102. The inhibition of kinase activity reduces YB-1 phosphorylation and its accumulation in the nucleus. The presence of RNA in the nucleus is shown to be required for the nuclear retention of YB-1. Thus, the subcellular localization of YB-1 depends on its post-translational modifications (PTMs) and intracellular RNA distribution.


2010 ◽  
Vol 30 (21) ◽  
pp. 4996-5008 ◽  
Author(s):  
G. Renuka Kumar ◽  
Britt A. Glaunsinger

ABSTRACT Poly(A) tail length is emerging as an important marker of mRNA fate, where deviations from the canonical length can signal degradation or nuclear retention of transcripts. Pathways regulating polyadenylation thus have the potential to broadly influence gene expression. Here we demonstrate that accumulation of cytoplasmic poly(A) binding protein (PABPC) in the nucleus, which can occur during viral infection or other forms of cellular stress, causes mRNA hyperadenylation and nuclear accumulation of poly(A) RNA. This inhibits gene expression but does not affect mRNA stability. Unexpectedly, PABPC-induced hyperadenylation can occur independently of mRNA 3′-end processing yet requires the canonical mRNA poly(A) polymerase II. We find that nuclear PABPC-induced hyperadenylation is triggered by multiple divergent viral factors, suggesting that altering the subcellular localization of PABPC may be a commonly used mechanism to regulate cellular gene expression in a polyadenylation-linked manner.


1991 ◽  
Vol 266 (24) ◽  
pp. 16188-16192 ◽  
Author(s):  
M.E. Lee ◽  
D.H. Temizer ◽  
J.A. Clifford ◽  
T. Quertermous

Planta ◽  
2021 ◽  
Vol 253 (2) ◽  
Author(s):  
Elysabeth K. Barnes ◽  
Moonhyuk Kwon ◽  
Connor L. Hodgins ◽  
Yang Qu ◽  
Seon-Won Kim ◽  
...  

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.


Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2739 ◽  
Author(s):  
Korbinian Benz ◽  
Andreas Schöbel ◽  
Marisa Dietz ◽  
Peter Maurer ◽  
Jochen Jackowski

The aim of this in vitro pilot study was to analyse the adhesion behaviour of human osteoblasts and fibroblasts on polyether ether ketone (PEEK) when compared with titanium surfaces in an inflammatory environment under lipopolysaccharide (LPS) incubation. Scanning electron microscopy (SEM) images of primary human osteoblasts/fibroblasts on titanium/PEEK samples were created. The gene expression of the LPS-binding protein (LBP) and the LPS receptor (toll-like receptor 4; TLR4) was measured by real-time polymerase chain reaction (PCR). Immunocytochemistry was used to obtain evidence for the distribution of LBP/TLR4 at the protein level of the extra-cellular-matrix-binding protein vinculin and the actin cytoskeleton. SEM images revealed that the osteoblasts and fibroblasts on the PEEK surfaces had adhesion characteristics comparable to those of titanium. The osteoblasts contracted under LPS incubation and a significantly increased LBP gene expression were detected. This was discernible at the protein level on all the materials. Whereas no increase of TLR4 was detected with regard to mRNA concentrations, a considerable increase in the antibody reaction was detected on all the materials. As is the case with titanium, the colonisation of human osteoblasts and fibroblasts on PEEK samples is possible under pro-inflammatory environmental conditions and the cellular inflammation behaviour towards PEEK is lower than that of titanium.


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