scholarly journals Lin28, a major translation reprogramming factor, gains access to YB-1-packaged mRNA through its cold-shock domain

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiia Samsonova ◽  
Krystel El Hage ◽  
Bénédicte Desforges ◽  
Vandana Joshi ◽  
Marie-Jeanne Clément ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cold Shock ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Large Set ◽  
Core Component ◽  
The Core ◽  
Cold Shock Domain ◽  
Global Translation

AbstractThe RNA-binding protein Lin28 (Lin28a) is an important pluripotency factor that reprograms translation and promotes cancer progression. Although Lin28 blocks let-7 microRNA maturation, Lin28 also binds to a large set of cytoplasmic mRNAs directly. However, how Lin28 regulates the processing of many mRNAs to reprogram global translation remains unknown. We show here, using a structural and cellular approach, a mixing of Lin28 with YB-1 (YBX1) in the presence of mRNA owing to their cold-shock domain, a conserved β-barrel structure that binds to ssRNA cooperatively. In contrast, the other RNA binding-proteins without cold-shock domains tested, HuR, G3BP-1, FUS and LARP-6, did not mix with YB-1. Given that YB-1 is the core component of dormant mRNPs, a model in which Lin28 gains access to mRNPs through its co-association with YB-1 to mRNA may provide a means for Lin28 to reprogram translation. We anticipate that the translational plasticity provided by mRNPs may contribute to Lin28 functions in development and adaptation of cancer cells to an adverse environment.

piRNAs Interact with Cold-Shock Domain-Containing RNA Binding Proteins and Regulate Neuronal Gene Expression During Differentiation

2022 ◽  
Author(s):  
Charannya Sozheesvari Subhramanyam ◽  
Qiong Cao ◽  
Cheng Wang ◽  
Zealyn Shi-Lin Heng ◽  
Zhihong Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Cold Shock ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Neuronal Gene ◽  
Cold Shock Domain

CSDC2, a cold shock domain RNA-binding protein in decidualization

2018 ◽  
Vol 234 (1) ◽  
pp. 740-748 ◽  
Author(s):  
Griselda Vallejo ◽  
Ana Cecilia Mestre-Citrinovitz ◽  
Elke Winterhager ◽  
Patricia Esther Saragüeta
Keyword(s):  
Cold Shock ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cold Shock Domain

scholarly journals MAC5, an RNA-binding protein, protects pri-miRNAs from SERRATE-dependent exoribonuclease activities

2020 ◽  
Vol 117 (38) ◽  
pp. 23982-23990 ◽  
Author(s):  
Shengjun Li ◽  
Mu Li ◽  
Kan Liu ◽  
Huimin Zhang ◽  
Shuxin Zhang ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Protein ◽  
Dual Role ◽  
Mirna Biogenesis ◽  
Core Component ◽  
Stem Loop ◽  
Loop Region ◽  
Nuclear Rna ◽  
Efficient Processing ◽  
The Stability

MAC5 is a component of the conserved MOS4-associated complex. It plays critical roles in development and immunity. Here we report that MAC5 is required for microRNA (miRNA) biogenesis. MAC5 interacts with Serrate (SE), which is a core component of the microprocessor that processes primary miRNA transcripts (pri-miRNAs) into miRNAs and binds the stem-loop region of pri-miRNAs. MAC5 is essential for both the efficient processing and the stability of pri-miRNAs. Interestingly, the reduction of pri-miRNA levels inmac5is partially caused by XRN2/XRN3, the nuclear-localized 5′-to-3′ exoribonucleases, and depends on SE. These results reveal that MAC5 plays a dual role in promoting pri-miRNA processing and stability through its interaction with SE and/or pri-miRNAs. This study also uncovers that pri-miRNAs need to be protected from nuclear RNA decay machinery, which is connected to the microprocessor.

scholarly journals The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mitochondrial Dysfunction ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Therapeutic Strategies ◽  
Lateral Sclerosis

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.

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 The Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyun Chen ◽  
Jianwen Yin ◽  
Dayan Cao ◽  
Deyong Xiao ◽  
Zhongjun Zhou ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Property ◽  
Cardiovascular Development ◽  
Potential Link ◽  
Alternatively Spliced ◽  
Unique Cell ◽  
Carboxy Terminal ◽  
And Function

RNA binding proteins (RBPs) have a broad biological and physiological function and are critical in regulating pre-mRNA posttranscriptional processing, intracellular migration, and mRNA stability. QKI, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family, which also belongs to the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. There are three major alternatively spliced isoforms, QKI-5, QKI-6, and QKI-7, differing in carboxy-terminal domains. They share a common RNA binding property, but each isoform can regulate pre-mRNA splicing, transportation or stability differently in a unique cell type-specific manner. Previously, QKI has been known for its important role in contributing to neurological disorders. A series of recent work has further demonstrated that QKI has important roles in much broader biological systems, such as cardiovascular development, monocyte to macrophage differentiation, bone metabolism, and cancer progression. In this mini-review, we will focus on discussing the emerging roles of QKI in regulating cardiac and vascular development and function and its potential link to cardiovascular pathophysiology.

scholarly journals Csde1 binds transcripts involved in protein homeostasis and controls their expression in erythropoiesis

2017 ◽  
Author(s):  
Kat S Moore ◽  
Nurcan Yagci ◽  
Floris van Alphen ◽  
Nahuel A Paolini ◽  
Rastislav Horos ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mrna Stability ◽  
Cold Shock ◽  
Rna Binding ◽  
Mrna Translation ◽  
Mitochondrial Respiratory Chain ◽  
Protein Homeostasis ◽  
Diamond Blackfan Anemia ◽  
Cold Shock Domain

AbstractExpression of the RNA-binding protein Csde1 (Cold shock domain protein e1) is strongly upregulated during erythropoiesis compared to other hematopoietic lineages. In the severe congenital anemia Diamond Blackfan Anemia (DBA), however, Csde1 expression is impaired. Reduced expression of Csde1 in healthy erythroblasts impaired their proliferation and differentiation, which suggests an important role for Csde1 in erythropoiesis. To investigate the cellular pathways controlled by Csde1 in erythropoiesis, we identified the transcripts that physically associate with Csde1 in erythroid cells. These mainly encoded proteins involved in ribogenesis, mRNA translation and protein degradation, but also proteins associated with the mitochondrial respiratory chain and mitosis. Crispr/Cas9-mediated deletion of the first cold shock domain of Csde1 affected RNA expression and/or protein expression of Csde1-bound transcripts. For instance, protein expression of Pabpc1 was enhanced while Pabpc1 mRNA expression was reduced indicating more efficient translation of Pabpc1 followed by negative feedback on mRNA stability. Overall, the effect of reduced Csde1 function on mRNA stability and translation of Csde1-bound transcripts was modest. Clones with complete loss of Csde1, however, could not be generated. We suggest that Csde1 is involved in feed-back control in protein homeostasis and that it dampens stochastic changes in mRNA expression.

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

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