scholarly journals The target specificity of the RNA binding protein Pumilio is determined by distinct co-factors

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Sumira Malik ◽  
Wijeong Jang ◽  
Song Yeon Park ◽  
Ji Young Kim ◽  
Ki-Sun Kwon ◽  
...  
Keyword(s):  
Cell Fate ◽  
Rna Binding ◽  
Neural Function ◽  
Target Specificity ◽  
Family Protein ◽  
Wide Range ◽  
Bag Of Marbles ◽  
Translational Regulators ◽  
Underlying Mechanisms ◽  
Puf Family

Abstract Puf family proteins are translational regulators essential to a wide range of biological processes, including cell fate specification, stem cell self-renewal, and neural function. Yet, despite being associated with hundreds of RNAs, the underlying mechanisms of Puf target specification remain to be fully elucidated. In Drosophila, Pumilio – a sole Puf family protein – is known to collaborate with cofactors Nanos (Nos) and Brain Tumor (Brat); however, their roles in target specification are not clearly defined. Here, we identify Bag-of-marbles (Bam) as a new Pum cofactor in repression of Mothers against dpp (mad) mRNAs, for which Nos is known to be dispensable. Notably, our data show that Nos (but not Bam) was required for Pum association with hunchback (hb) mRNAs, a well-known target of Pum and Nos. In contrast, Bam (but not Nos) was required for Pum association with mad mRNAs. These findings show for the first time that Pum target specificity is determined not independently but in collaboration with cofactors.

scholarly journals Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination

2021 ◽  
Vol 22 (24) ◽  
pp. 13338
Author(s):  
Qing Zhang ◽  
Jin Jiang
Keyword(s):  
Signal Transduction ◽  
Transmembrane Protein ◽  
Cubitus Interruptus ◽  
Congenital Diseases ◽  
Gli Proteins ◽  
Family Protein ◽  
Wide Range ◽  
Human Disorders ◽  
Underlying Mechanisms ◽  
Hedgehog Signal

The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis in species ranging from insects to mammals. Deregulation of Hh pathway activity has been implicated in a wide range of human disorders, including congenital diseases and cancer. Hh exerts its biological influence through a conserved signaling pathway. Binding of Hh to its receptor Patched (Ptc), a twelve-span transmembrane protein, leads to activation of an atypical GPCR family protein and Hh signal transducer Smoothened (Smo), which then signals downstream to activate the latent Cubitus interruptus (Ci)/Gli family of transcription factors. Hh signal transduction is regulated by ubiquitination and deubiquitination at multiple steps along the pathway including regulation of Ptc, Smo and Ci/Gli proteins. Here we review the effect of ubiquitination and deubiquitination on the function of individual Hh pathway components, the E3 ubiquitin ligases and deubiquitinases involved, how ubiquitination and deubiquitination are regulated, and whether the underlying mechanisms are conserved from Drosophila to mammals.

scholarly journals A Gene Expressed during Sexual and Asexual Sporulation in Phytophthora infestans Is a Member of the Puf Family of Translational Regulators

2003 ◽  
Vol 2 (3) ◽  
pp. 465-473 ◽  
Author(s):  
Cristina Cvitanich ◽  
Howard S. Judelson
Keyword(s):  
Amino Acid ◽  
Phytophthora Infestans ◽  
Rna Binding ◽  
Amino Acid Identity ◽  
Puf Proteins ◽  
Asexual Sporulation ◽  
Gus Reporter ◽  
The Family ◽  
Translational Regulators ◽  
Puf Family

ABSTRACT A gene from Phytophthora infestans that was previously identified as being induced during the development of sexual spores was also found to be active during asexual sporulation. The gene, M90, was expressed as a 3.1-kb primary transcript containing two introns and was predicted to encode a member of the Puf family of translational regulators. The protein showed up to 51% amino acid identity to other Puf proteins within its 353-amino-acid RNA-binding domain. Little similarity extended beyond this region, as noted for other members of the family. Expression of M90 was measured by using RNA blots and transformants of P. infestans expressing a fusion between the M90 promoter and the β-glucuronidase (GUS) gene. A 1.3-kb promoter fragment conferred the normal M90 pattern of expression to the GUS reporter in transformants. In matings, expression was first detected in male and female gametangial initials and persisted in mature oospores. Expression was also observed in hyphal tips just prior to asexual sporulation, in sporangiophores, in mature sporangia, and in zoospores. The signal quickly disappeared once spores made the transition to hyphae after germination. Nutrient limitation did not induce the gene. Potential roles for a translational regulator during both sexual development and asexual sporulation are discussed.

scholarly journals Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Chih-Yung Sean Lee ◽  
Tu Lu ◽  
Geraldine Seydoux
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Activation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Primordial Germ Cells ◽  
Germline Development ◽  
C Elegans ◽  
Maternal Transcripts ◽  
Underlying Mechanisms

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

scholarly journals Regulatory network control of blood stem cells

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2614-2620 ◽  
Author(s):  
Berthold Göttgens
Keyword(s):  
Decision Making ◽  
Stem Cells ◽  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Types ◽  
Network Control ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Fate Decision ◽  
Underlying Mechanisms

Abstract Hematopoietic stem cells (HSCs) are characterized by their ability to execute a wide range of cell fate choices, including self-renewal, quiescence, and differentiation into the many different mature blood lineages. Cell fate decision making in HSCs, as indeed in other cell types, is driven by the interplay of external stimuli and intracellular regulatory programs. Given the pivotal nature of HSC decision making for both normal and aberrant hematopoiesis, substantial research efforts have been invested over the last few decades into deciphering some of the underlying mechanisms. Central to the intracellular decision making processes are transcription factor proteins and their interactions within gene regulatory networks. More than 50 transcription factors have been shown to affect the functionality of HSCs. However, much remains to be learned about the way in which individual factors are connected within wider regulatory networks, and how the topology of HSC regulatory networks might affect HSC function. Nevertheless, important progress has been made in recent years, and new emerging technologies suggest that the pace of progress is likely to accelerate. This review will introduce key concepts, provide an integrated view of selected recent studies, and conclude with an outlook on possible future directions for this field.

scholarly journals Release mechanisms of major DAMPs

APOPTOSIS ◽  
2021 ◽  
Vol 26 (3-4) ◽  
pp. 152-162
Author(s):  
Atsushi Murao ◽  
Monowar Aziz ◽  
Haichao Wang ◽  
Max Brenner ◽  
Ping Wang
Keyword(s):  
Rna Binding ◽  
High Mobility ◽  
Live Cells ◽  
Membrane Channel ◽  
Membrane Rupture ◽  
Underlying Mechanisms ◽  
Shock Proteins ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Secretory Lysosomes

AbstractDamage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

scholarly journals The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities

2021 ◽  
Vol 22 (13) ◽  
pp. 6857
Author(s):  
Samantha Bruno ◽  
Manuela Mancini ◽  
Sara De Santis ◽  
Cecilia Monaldi ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cell Fate ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Bone Marrow Microenvironment ◽  
Metabolic Adaptation ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.

scholarly journals Parasites—the new frontier: celebrating Darwin 200

2009 ◽  
Vol 5 (5) ◽  
pp. 625-627 ◽  
Author(s):  
Paul Schmid-Hempel
Keyword(s):  
Population Biology ◽  
Life Histories ◽  
Evolutionary Ecology ◽  
Adaptive Value ◽  
Wide Range ◽  
New Frontier ◽  
Underlying Mechanisms ◽  
The One ◽  
Immune Defences ◽  
Recurrent Theme

To Darwin, parasites were fascinating examples of adaptation but their significance as selective factors for a wide range of phenomena has only been studied in depth over the last few decades. This work has had its roots in behavioural/evolutionary ecology on the one hand, and in population biology/ecology on the other, thus shaping a new comprehensive field of ‘evolutionary parasitology’. Taking parasites into account has been a success story and has shed new light on several old questions such as sexual selection, the evolution of sex and recombination, changes in behaviour, adaptive life histories, and so forth. In the process, the topic of ecological immunology has emerged, which analyses immune defences in a framework of costs and benefits. Throughout, a recurrent theme is how to appropriately integrate the underlying mechanisms as evolved boundary conditions into a framework of studying the adaptive value of traits. On the conceptual side, major questions remain and await further study.

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