scholarly journals Multi-Level Regulatory Interactions between NF-κB and the Pluripotency Factor Lin28

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2710
Author(s):  
William T. Mills ◽  
Noor N. Nassar ◽  
Deepa Ravindra ◽  
Xinbei Li ◽  
Mollie K. Meffert
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Future Directions ◽  
Regulatory Interactions ◽  
Master Regulators ◽  
The Past ◽  
Complex Interactions ◽  
Multi Level ◽  
Signaling Interactions

An appreciation for the complex interactions between the NF-κB transcription factor and the Lin28 RNA binding protein/let-7 microRNA pathways has grown substantially over the past decade. Both the NF-κB and Lin28/let-7 pathways are master regulators impacting cell survival, growth and proliferation, and an understanding of how interfaces between these pathways participate in governing pluripotency, progenitor differentiation, and neuroplastic responses remains an emerging area of research. In this review, we provide a concise summary of the respective pathways and focus on the function of signaling interactions at both the transcriptional and post-transcriptional levels. Regulatory loops capable of providing both reinforcing and extinguishing feedback have been described. We highlight convergent findings in disparate biological systems and indicate future directions for investigation.

scholarly journals Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

2017 ◽  
Author(s):  
Chih-Yung S. Lee ◽  
Tu Lu ◽  
Geraldine Seydoux
Keyword(s):  
Transcription Factor ◽  
Germ Cells ◽  
Rna Binding ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Rna Binding Protein ◽  
Dependent Manner ◽  
Embryonic Cells ◽  
C Elegans ◽  
Underlying Mechanisms

AbstractThe Nanos RNA-binding protein has been implicated in the specification of primordial germ cells (PGCs) in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 iC. elegans. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of PGCs away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity.

scholarly journals Regulatory Interactions of Csr Components: the RNA Binding Protein CsrA Activates csrB Transcription inEscherichia coli

2001 ◽  
Vol 183 (20) ◽  
pp. 6017-6027 ◽  
Author(s):  
Seshagirirao Gudapaty ◽  
Kazushi Suzuki ◽  
Xin Wang ◽  
Paul Babitzke ◽  
Tony Romeo
Keyword(s):  
Rna Binding ◽  
Binding Capacity ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Growth Curves ◽  
Regulatory Interactions ◽  
Transcript Stability ◽  
Carbon Storage Regulator

ABSTRACT The global regulator CsrA (carbon storage regulator) ofEscherichia coli is a small RNA binding protein that represses various metabolic pathways and processes that are induced in the stationary phase of growth, while it activates certain exponential phase functions. Both repression and activation by CsrA involve posttranscriptional mechanisms, in which CsrA binding to mRNA leads to decreased or increased transcript stability, respectively. CsrA also binds to a small untranslated RNA, CsrB, forming a ribonucleoprotein complex, which antagonizes CsrA activity. We have further examined the regulatory interactions of CsrA and CsrB RNA. The 5′ end of the CsrB transcript was mapped, and acsrB::cam null mutant was constructed. CsrA protein and CsrB RNA levels were estimated throughout the growth curves of wild-type and isogenic csrA,csrB, rpoS, or csrA rpoSmutant strains. CsrA levels exhibited modest or negligible effects of these mutations. The intracellular concentration of CsrA exceeded the total CsrA-binding capacity of intracellular CsrB RNA. In contrast, CsrB levels were drastically decreased (∼10-fold) in thecsrA mutants. CsrB transcript stability was unaffected by csrA. The expression of a csrB-lacZtranscriptional fusion containing the region from −242 to +4 bp of thecsrB gene was decreased ∼20-fold by acsrA::kanR mutation in vivo but was unaffected by CsrA protein in vitro. These results reveal a significant, though most likely indirect, role for CsrA in regulatingcsrB transcription. Furthermore, our findings suggest that CsrA mediates an intriguing form of autoregulation, whereby its activity, but not its levels, is modulated through effects on an RNA antagonist, CsrB.

scholarly journals Polyamines Regulate the Stability of Activating Transcription Factor-2 mRNA through RNA-binding Protein HuR in Intestinal Epithelial Cells

2007 ◽  
Vol 18 (11) ◽  
pp. 4579-4590 ◽  
Author(s):  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Bernard S. Marasa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Gene Promoter ◽  
Protein Levels ◽  
Ribonucleoprotein Complexes ◽  
Activating Transcription Factor ◽  
The Stability

Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR. Here, we show that polyamines negatively regulate ATF-2 expression posttranscriptionally and that polyamine depletion stabilizes ATF-2 mRNA by enhancing the interaction of the 3′-untranslated region (UTR) of ATF-2 with cytoplasmic HuR. Decreasing cellular polyamines by inhibiting ornithine decarboxylase (ODC) with α-difluoromethylornithine increased the levels of ATF-2 mRNA and protein, whereas increasing polyamines by ectopic ODC overexpression repressed ATF-2 expression. Polyamine depletion did not alter transcription via the ATF-2 gene promoter but increased the stability of ATF-2 mRNA. Increased cytoplasmic HuR in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous ATF-2 mRNA and specifically bound to 3′-UTR of ATF-2 mRNA on multiple nonoverlapping 3′-UTR segments. Adenovirus-mediated HuR overexpression elevated ATF-2 mRNA and protein levels, whereas HuR silencing rendered the ATF-2 mRNA unstable and prevented increases in ATF-2 mRNA and protein. Furthermore, inhibition of ATF-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-α and cycloheximide. These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis.

scholarly journals C/EBPα acts as an RNA binding protein essential for its chromatin recruitment and promotes Macrophage differentiation

2021 ◽  
Author(s):  
Yanzhou Zhang ◽  
Mahmoud Bassal ◽  
Daniel Friedrich ◽  
Simone Ummarino ◽  
Tom Verbiest ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Specific Gene ◽  
Macrophage Differentiation ◽  
Binding Domains ◽  
Rna Binding Domains ◽  
Neutrophil Differentiation

C/EBPα has known to be a transcription factor that involved in Neutrophil differentiation for decades. However, exploring the Chromatin RNA Immunoprecipitation Sequencing (RIP), we discover that C/EBPα is a RNA binding protein mainly interacts with RNA introns. Structure study and RNA electrophoretic mobility shift assay (REMSA) show that C/EBPα interacts with RNA through two novel RNA binding domains distinct from its DNA binding domain. Mouse bone marrow transplantation and in vitro cytokine assay reveal that C/EBPα RNA binding is critical for Macrophage differentiation but not Neutrophil differentiation. Mechanically, RNA binding domains control specific gene transcription. In particular, PU.1 intron 4 RNA interacts with C/EBPα and recruit C/EBPα to its enhancer site, which facilitate PU.1 expression. Taken together, C/EBPα is demonstrated to be a RNA binding protein with unique function distinct from its DNA binding activity. Our finding transforms our knowledge of transcriptional regulation by transcription factor.

scholarly journals RNA Binding Protein, HuR, Regulates SCN5A Expression Through Stabilizing MEF2C transcription factor mRNA

2018 ◽  
Vol 7 (9) ◽  
Author(s):  
Anyu Zhou ◽  
Guangbin Shi ◽  
Gyeoung‐Jin Kang ◽  
An Xie ◽  
Hong Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Two parallel arms of the heterochronic pathway direct coordinated juvenile-to-adult transition through distinct LIN-29 isoforms

2019 ◽  
Author(s):  
Chiara Azzi ◽  
Florian Aeschimann ◽  
Anca Neagu ◽  
Helge Großhans
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Expression Patterns ◽  
Rna Binding Protein ◽  
Adult Transition ◽  
Physiological Processes ◽  
Regulatory Cascade ◽  
The Individual ◽  
Organismal Development

AbstractRobust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the timely transition from juvenile to adult is controlled by the heterochronic pathway, a regulatory cascade of conserved proteins and small RNAs. The heterochronic pathway culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of juvenile-to-adult (J/A) transition events. Here, we reveal that two LIN-29 isoforms fulfill distinct functions during the J/A transition. We show that the functional differences between the isoforms do not stem from differences in their sequences, but from their distinct spatiotemporal expression, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique lin-29 isoform expression patterns are generated by the RNA-binding protein LIN-41 for lin-29a, and the transcription factor HBL-1 for lin-29b. By regulating both HBL-1 and LIN-41, the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity. Thus, our findings reveal that a coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

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