scholarly journals Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells

2019 ◽  
Author(s):  
Samudyata ◽  
Paulo P. Amaral ◽  
Pär G. Engström ◽  
Samuel C. Robson ◽  
Michael L. Nielsen ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Embryonic Stem ◽  
Messenger Rnas ◽  
Heterochromatin Protein 1 ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Mes Cells

AbstractSox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role of Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interact with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but might rather regulate other processes in the nucleoplasm.Summary blurbSox2 interacts with RNA-binding proteins and diverse RNAs

scholarly journals RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts

2018 ◽  
Vol 48 (3) ◽  
pp. 1215-1229 ◽  
Author(s):  
Sihyung Wang ◽  
Youngmi Jung ◽  
Jeongeun Hyun ◽  
Matthew Friedersdorf ◽  
Seh-Hoon Oh ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Stellate Cells ◽  
Fibrous Matrix ◽  
Rna Immunoprecipitation ◽  
Physical Interactions ◽  
Β Receptor ◽  
Dependent Mechanism

Background/Aims: Myofibroblasts (MF) derived from quiescent nonfibrogenic hepatic stellate cells (HSC) are the major sources of fibrous matrix in cirrhosis. Because many factors interact to regulate expansion and regression of MF-HSC populations, efforts to prevent cirrhosis by targeting any one factor have had limited success, motivating research to identify mechanisms that integrate these diverse inputs. As key components of RNA regulons, RNA binding proteins (RBPs) may fulfill this function by orchestrating changes in the expression of multiple genes that must be coordinately regulated to affect the complex phenotypic modifications required for HSC transdifferentiation. Methods: We profiled the transcriptomes of quiescent and MF-HSC to identify RBPs that were differentially-expressed during HSC transdifferentiation, manipulated the expression of the most significantly induced RBP, insulin like growth factor 2 binding protein 3 (Igf2bp3), and evaluated transcriptomic and phenotypic effects. Results: Depleting Igf2bp3 changed the expression of thousands of HSC genes, including multiple targets of TGF-β signaling, and caused HSCs to reacquire a less proliferative, less myofibroblastic phenotype. RNA immunoprecipitation assays demonstrated that some of these effects were mediated by direct physical interactions between Igf2bp3 and mRNAs that control proliferative activity and mesenchymal traits. Inhibiting TGF-β receptor-1 signaling revealed a microRNA-dependent mechanism that induces Igf2bp3. Conclusions: The aggregate results indicate that HSC transdifferentiation is ultimately dictated by Igf2bp3-dependent RNA regulons and thus, can be controlled simply by manipulating Igf2bp3.

scholarly journals Quantitative Proteomics to Identify Nuclear RNA-Binding Proteins of Malat1

2020 ◽  
Vol 21 (3) ◽  
pp. 1166 ◽  
Author(s):  
Marian Scherer ◽  
Michal Levin ◽  
Falk Butter ◽  
Marion Scheibe
Keyword(s):  
Quantitative Proteomics ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Full Length ◽  
Interacting Proteins ◽  
Non Coding Rna ◽  
Nuclear Rna ◽  
Long Non Coding Rna ◽  
Shed Light

The long non-coding RNA Malat1 has been implicated in several human cancers, while the mechanism of action is not completely understood. As RNAs in cells function together with RNA-binding proteins (RBPs), the composition of their RBP complex can shed light on their functionality. We here performed quantitative interactomics of 14 non-overlapping fragments covering the full length of Malat1 to identify possible nuclear interacting proteins. Overall, we identified 35 candidates including 14 already known binders, which are able to interact with Malat1 in the nucleus. Furthermore, the use of fragments along the full-length RNA allowed us to reveal two hotspots for protein binding, one in the 5′-region and one in the 3′-region of Malat1. Our results provide confirmation on previous RNA-protein interaction studies and suggest new candidates for functional investigations.

Advances in the identification of long non-coding RNA binding proteins

2021 ◽  
pp. 114520
Author(s):  
Dongqing Zhao ◽  
Chunqing Wang ◽  
Shuai Yan ◽  
Ruibing Chen
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Identification of RNA-binding proteins that partner with Lin28a to regulate Dnmt3a expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Silvia Parisi ◽  
Daniela Castaldo ◽  
Silvia Piscitelli ◽  
Chiara D’Ambrosio ◽  
Giuseppina Divisato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methyltransferase ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Embryonic Stem ◽  
Direct Interaction ◽  
Mirna Biogenesis ◽  
Dna Methyltransferase 3A

AbstractLin28 is an evolutionary conserved RNA-binding protein that plays important roles during embryonic development and tumorigenesis. It regulates gene expression through two different post-transcriptional mechanisms. The first one is based on the regulation of miRNA biogenesis, in particular that of the let-7 family, whose expression is suppressed by Lin28. Thus, loss of Lin28 leads to the upregulation of mRNAs that are targets of let-7 species. The second mechanism is based on the direct interaction of Lin28 with a large number of mRNAs, which results in the regulation of their translation. This second mechanism remains poorly understood. To address this issue, we purified high molecular weight complexes containing Lin28a in mouse embryonic stem cells (ESCs). Numerous proteins, co-purified with Lin28a, were identified by proteomic procedures and tested for their possible role in Lin28a-dependent regulation of the mRNA encoding DNA methyltransferase 3a (Dnmt3a). The results show that Lin28a activity is dependent on many proteins, including three helicases and four RNA-binding proteins. The suppression of four of these proteins, namely Ddx3x, Hnrnph1, Hnrnpu or Syncrip, interferes with the binding of Lin28a to the Dnmt3a mRNA, thus suggesting that they are part of an oligomeric ribonucleoprotein complex that is necessary for Lin28a activity.

scholarly journals RNA-Binding Proteins in Acute Leukemias

2020 ◽  
Vol 21 (10) ◽  
pp. 3409 ◽  
Author(s):  
Konstantin Schuschel ◽  
Matthias Helwig ◽  
Stefan Hüttelmaier ◽  
Dirk Heckl ◽  
Jan-Henning Klusmann ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genetic Diseases ◽  
Clinical Aspects ◽  
Translational Efficiency ◽  
Messenger Rnas ◽  
Acute Leukemias

Acute leukemias are genetic diseases caused by translocations or mutations, which dysregulate hematopoiesis towards malignant transformation. However, the molecular mode of action is highly versatile and ranges from direct transcriptional to post-transcriptional control, which includes RNA-binding proteins (RBPs) as crucial regulators of cell fate. RBPs coordinate RNA dynamics, including subcellular localization, translational efficiency and metabolism, by binding to their target messenger RNAs (mRNAs), thereby controlling the expression of the encoded proteins. In view of the growing interest in these regulators, this review summarizes recent research regarding the most influential RBPs relevant in acute leukemias in particular. The reported RBPs, either dysregulated or as components of fusion proteins, are described with respect to their functional domains, the pathways they affect, and clinical aspects associated with their dysregulation or altered functions.

scholarly journals TDP-43 and FUS RNA-binding Proteins Bind Distinct Sets of Cytoplasmic Messenger RNAs and Differently Regulate Their Post-transcriptional Fate in Motoneuron-like Cells

2012 ◽  
Vol 287 (19) ◽  
pp. 15635-15647 ◽  
Author(s):  
Claudia Colombrita ◽  
Elisa Onesto ◽  
Francesca Megiorni ◽  
Antonio Pizzuti ◽  
Francisco E. Baralle ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Messenger Rnas

scholarly journals The RNA-Binding Protein SAM68 regulates cardiomyocyte differentiation by enhancing Gata4 translation

2022 ◽  
Author(s):  
Alessandro Dasti ◽  
Maria Carla Antonelli ◽  
Magdalena Arnal Segura ◽  
Alexandros Armaos ◽  
Sarah Bonnin ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Embryonic Stem ◽  
Ribosome Profiling ◽  
Cardiomyocyte Differentiation ◽  
Mammalian Development ◽  
Mobility Shift ◽  
Lineage Specification ◽  
Rna Immunoprecipitation ◽  
Mobility Shift Assay

The signal transduction and activation of RNA (STAR) family is composed of RNA-binding proteins (RBPs) that play a central role in mammalian development. Nonetheless, the functions and modes of action that STAR proteins have in lineage specification are still poorly understood. Here, we characterized the role of STAR proteins SAM68 and QUAKING (QKI) in pluripotency and differentiation by performing their depletion through CRISPR-Cas9 in mouse embryonic stem cells (mESCs). Combining RNA-sequencing, ribosome profiling and advanced computational predictions, we found that both SAM68 and QKI regulate the mESCs self-renewal and are indispensable for cardiomyocyte differentiation. At the molecular level, we discovered that SAM68 and QKI antagonistically control the expression of cardiogenic factors. Our calculations indicated that SAM68, unlike QKI, binds the cardiogenic-specific transcription factor Gata4 in a region spanning nucleotides 500 to 1000 of the mRNA corresponding to part of the 5' untranslated region and the first exon. We validated the predictions by electrophoretic mobility shift assay and RNA immunoprecipitation showing that SAM68 controls the translation of Gata4 during mESCs differentiation towards the cardiomyocyte lineage.

scholarly journals The Combined Regulation of Long Non-coding RNA and RNA-Binding Proteins in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuanyuan Ding ◽  
Ruihua Yin ◽  
Shuai Zhang ◽  
Qi Xiao ◽  
Hongqin Zhao ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Specific Interaction ◽  
Clinical Issue ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Atherosclerosis is a complex disease closely related to the function of endothelial cells (ECs), monocytes/macrophages, and vascular smooth muscle cells (VSMCs). Despite a good understanding of the pathogenesis of atherosclerosis, the underlying molecular mechanisms are still only poorly understood. Therefore, atherosclerosis continues to be an important clinical issue worthy of further research. Recent evidence has shown that long non-coding RNAs (lncRNAs) and RNA-binding proteins (RBPs) can serve as important regulators of cellular function in atherosclerosis. Besides, several studies have shown that lncRNAs are partly dependent on the specific interaction with RBPs to exert their function. This review summarizes the important contributions of lncRNAs and RBPs in atherosclerosis and provides novel and comprehensible interaction models of lncRNAs and RBPs.

scholarly journals Advances in the identification of long non-coding RNA binding proteins

2021 ◽  
pp. 100010
Author(s):  
Dongqing Zhao ◽  
Chunqing Wang ◽  
Shuai Yan ◽  
Ruibing Chen
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Non Coding Rna ◽  
Long Non Coding Rna
Sign in / Sign up

Export Citation Format

Share Document