scholarly journals Berberine Promotes Beige Adipogenic Signatures of 3T3-L1 Cells by Regulating Post-transcriptional Events

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 632 ◽  
Author(s):  
Ying-Chin Lin ◽  
Yuan-Chii Lee ◽  
Ying-Ju Lin ◽  
Jung-Chun Lin
Keyword(s):  
Transcriptional Regulation ◽  
Rna Binding ◽  
Binding Motif ◽  
Gene Expressions ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Study Results ◽  
Beige Cells ◽  
Post Transcriptional Regulation ◽  
The Impact

Induced brown adipocytes (also referred to as beige cells) execute thermogenesis, as do the classical adipocytes by consuming stored lipids, being related to metabolic homeostasis. Treatment of phytochemicals, including berberine (BBR), was reported to induce conversion from white adipocytes to beige cells. In this study, results of microRNA (miRNA)-seq analyses revealed a decrease in miR-92a, of which the transcription is driven by the c13orf25 promoter in BBR-treated 3T3-L1 cells. BBR treatment manipulated the expressions of SP1 and MYC, in turn, reducing the activity of the c13orf25 promoter. A decrease in miR-92a led to an increase in RNA-binding motif protein 4a (RBM4a) expression, which facilitated the beige adipogenesis. Overexpression of miR-92a or depletion of RBM4a reversely interfered with the impact of BBR treatment on the beige adipogenic signatures, gene expressions, and splicing events in 3T3-L1 cells. Our findings demonstrated that BBR treatment enhanced beige adipogenesis of 3T3-L1 cells through transcription-coupled post-transcriptional regulation.

scholarly journals Post-transcriptional regulation of human endogenous retroviruses by RNA-Binding Motif Protein 4, RBM4

2020 ◽  
Author(s):  
Amir K. Foroushani ◽  
Bryan Chim ◽  
Madeline Wong ◽  
Andre Rastegar ◽  
Kent Barbian ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Human Genome ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Ectopic Expression ◽  
Endogenous Retroviruses ◽  
Binding Motif ◽  
Computational Pipeline ◽  
Post Transcriptional Regulation

AbstractThe human genome encodes for over 1,500 RNA-binding proteins (RBPs), which coordinate regulatory events on RNA transcripts (Gerstberger et al., 2014). Most studies of RBPs concentrate on their action on mRNAs that encode protein, which constitute a minority of the transcriptome. A widely neglected subset of our transcriptome derives from integrated retroviral elements termed endogenous retroviruses (ERVs) that comprise ~8% of the human genome. Some ERVs have been shown to be transcribed under physiological and pathological conditions suggesting that sophisticated regulatory mechanisms to coordinate and prevent their ectopic expression exist. However, it is unknown whether RBPs and ERV transcripts directly interact to provide a post-transcriptional layer of regulation. Here, we implemented a computational pipeline to determine the correlation of expression between individual RBPs and ERVs from single-cell or bulk RNA sequencing data. One of our top candidates for an RBP negatively regulating ERV expression was RNA-Binding Motif Protein 4 (RBM4). We used PAR-CLIP to demonstrate that RBM4 indeed bound ERV transcripts at CGG consensus elements. Loss of RBM4 resulted in elevated transcript level of bound ERVs of the HERV-K and -H families, as well as increased expression of HERV-K envelope protein. We pinpointed RBM4 regulation of HERV-K to a CGG-containing element that is conserved in the long terminal repeats (LTRs) of HERV-K-10 and -K-11, and validated the functionality of this site using reporter assays. In summary, we identified RBPs as potential regulators of ERV function and demonstrate a new role for RBM4 in controlling ERV expression.Significance StatementThe expression of endogenous retroviruses (ERVs) appears to have broad impact on human biology. Nevertheless, only a handful of transcriptional regulators of ERV expression are known and to our knowledge no RNA-binding proteins (RBPs) were yet implicated in positive or negative post-transcriptional regulation of ERVs. We implemented a computational pipeline that allowed us to identify RBPs that modulate ERV expression levels. Experimental validation of one of the prime candidates we identified, RBM4, showed that it indeed bound RNAs made from ERVs and negatively regulated the levels of those RNAs. We hereby identify a new layer of ERV regulation by RBPs.

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control

2019 ◽  
Vol 97 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Laura P.M.H. de Rooij ◽  
Derek C.H. Chan ◽  
Ava Keyvani Chahi ◽  
Kristin J. Hope
Keyword(s):  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cell Fate ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Control Of Gene Expression ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Post Transcriptional Regulation

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

scholarly journals Aberrant Post-Transcriptional Regulation of Protein Expression in the Development of Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 22 (21) ◽  
pp. 11963
Author(s):  
Noof Aloufi ◽  
Aeshah Alluli ◽  
David H. Eidelman ◽  
Carolyn J. Baglole
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Transcriptional Regulation ◽  
Pulmonary Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Chronic Obstructive ◽  
Respiratory Disorder ◽  
Obstructive Pulmonary Disease ◽  
Cellular Processes ◽  
Post Transcriptional Regulation

Chronic obstructive pulmonary disease (COPD) is an incurable and prevalent respiratory disorder that is characterized by chronic inflammation and emphysema. COPD is primarily caused by cigarette smoke (CS). CS alters numerous cellular processes, including the post-transcriptional regulation of mRNAs. The identification of RNA-binding proteins (RBPs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as main factors engaged in the regulation of RNA biology opens the door to understanding their role in coordinating physiological cellular processes. Dysregulation of post-transcriptional regulation by foreign particles in CS may lead to the development of diseases such as COPD. Here we review current knowledge about post-transcriptional events that may be involved in the pathogenesis of COPD.

The impact of epitranscriptomic marks on post-transcriptional regulation in plants

2020 ◽  
Author(s):  
Xiang Yu ◽  
Bishwas Sharma ◽  
Brian D Gregory
Keyword(s):  
Transcriptional Regulation ◽  
Plant Development ◽  
Messenger Rna ◽  
Rna Modifications ◽  
Abiotic And Biotic Stresses ◽  
Rna Molecules ◽  
Biotic Stresses ◽  
Specific Mrnas ◽  
Post Transcriptional Regulation ◽  
The Impact

Abstract Ribonucleotides within the various RNA molecules in eukaryotes are marked with more than 160 distinct covalent chemical modifications. These modifications include those that occur internally in messenger RNA (mRNA) molecules such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), as well as those that occur at the ends of the modified RNAs like the non-canonical 5′ end nicotinamide adenine dinucleotide (NAD+) cap modification of specific mRNAs. Recent findings have revealed that covalent RNA modifications can impact the secondary structure, translatability, functionality, stability and degradation of the RNA molecules in which they are included. Many of these covalent RNA additions have also been found to be dynamically added and removed through writer and eraser complexes, respectively, providing a new layer of epitranscriptome-mediated post-transcriptional regulation that regulates RNA quality and quantity in eukaryotic transcriptomes. Thus, it is not surprising that the regulation of RNA fate mediated by these epitranscriptomic marks has been demonstrated to have widespread effects on plant development and the responses of these organisms to abiotic and biotic stresses. In this review, we highlight recent progress focused on the study of the dynamic nature of these epitranscriptome marks and their roles in post-transcriptional regulation during plant development and response to environmental cues, with an emphasis on the mRNA modifications of non-canonical 5′ end NAD+ capping, m6A and several other internal RNA modifications.

scholarly journals Involvement of ELAV RNA-binding proteins in the post-transcriptional regulation of HO-1

2015 ◽  
Vol 8 ◽  
Author(s):  
Marialaura Amadio ◽  
Giovanni Scapagnini ◽  
Sergio Davinelli ◽  
Vittorio Calabrese ◽  
Stefano Govoni ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Post Transcriptional Regulation

scholarly journals Ribosome-Profiling Reveals Restricted Post Transcriptional Expression of Antiviral Cytokines and Transcription Factors during SARS-CoV-2 Infection

2021 ◽  
Vol 22 (7) ◽  
pp. 3392
Author(s):  
Marina R. Alexander ◽  
Aaron M. Brice ◽  
Petrus Jansen van Vuren ◽  
Christina L. Rootes ◽  
Leon Tribolet ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Host Response ◽  
High Viral Load ◽  
Ribosome Profiling ◽  
Epithelial Cell Line ◽  
Transcriptional Level ◽  
Human Lung Epithelial Cell ◽  
Post Transcriptional Regulation ◽  
The Impact

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here, we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.

scholarly journals RNA-binding proteins involved in post-transcriptional regulation in bacteria

2015 ◽  
Vol 6 ◽  
Author(s):  
Elke Van Assche ◽  
Sandra Van Puyvelde ◽  
Jos Vanderleyden ◽  
Hans P. Steenackers
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Post Transcriptional Regulation
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