scholarly journals L-bodies are novel RNA-protein condensates driving RNA transport in Xenopus oocytes

2020 ◽  
Author(s):  
Christopher R. Neil ◽  
Samantha P. Jeschonek ◽  
Sarah E. Cabral ◽  
Liam C. O’Connell ◽  
Erin A. Powrie ◽  
...  
Keyword(s):  
Rna Localization ◽  
Biological Processes ◽  
Rna Transport ◽  
Embryonic Patterning ◽  
New Class ◽  
Granule Structure ◽  
Maternal Mrnas ◽  
And Function ◽  
Rnp Granules

AbstractRNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are transported as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that vegetal transport RNPs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies are multiphase RNP granules, containing a dynamic protein-containing phase surrounding a non-dynamic RNA-containing substructure. Our results support a role for RNA as a critical scaffold component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.

scholarly journals L-bodies are RNA-protein condensates driving RNA localization in Xenopus oocytes

2021 ◽  
Author(s):  
Christopher R. Neil ◽  
Samantha P. Jeschonek ◽  
Sarah E. Cabral ◽  
Liam C. O'Connell ◽  
Erin A. Powrie ◽  
...  
Keyword(s):  
Rna Localization ◽  
Xenopus Laevis Oocytes ◽  
Biological Processes ◽  
Embryonic Patterning ◽  
New Class ◽  
Granule Structure ◽  
Maternal Mrnas ◽  
And Function ◽  
Rnp Granules

RNP granules are membrane-less compartments within cells, formed by phase separation, that function as regulatory hubs for diverse biological processes. However, the mechanisms by which RNAs and proteins interact to promote RNP granule structure and function in vivo remain unclear. In Xenopus laevis oocytes, maternal mRNAs are localized as large RNPs to the vegetal hemisphere of the developing oocyte, where local translation is critical for proper embryonic patterning. Here, we demonstrate that RNPs containing vegetally localized RNAs represent a new class of cytoplasmic RNP granule, termed Localization-bodies (L-bodies). We show that L-bodies contain a dynamic protein-containing phase surrounding a non-dynamic RNA-containing phase. Our results support a role for RNA as a critical component within these RNP granules and suggest that cis-elements within localized mRNAs may drive subcellular RNA localization through control over phase behavior.

scholarly journals C. elegans germ granules require both assembly and localized regulators for mRNA repression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Scott Takeo Aoki ◽  
Tina R. Lynch ◽  
Sarah L. Crittenden ◽  
Craig A. Bingman ◽  
Marvin Wickens ◽  
...  
Keyword(s):  
Liquid Droplet ◽  
Scaffolding Protein ◽  
P Granules ◽  
C Elegans ◽  
Cytoplasmic Rna ◽  
And Function ◽  
Rnp Granules ◽  
Key Residues ◽  
Reporter Mrna

AbstractCytoplasmic RNA–protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P granule scaffolding protein, PGL-1, to investigate the functional relationship between P granule assembly and function. Using a protein–RNA tethering assay, we find that reporter mRNA expression is repressed when recruited to PGL-1. We determine the crystal structure of the PGL-1 N-terminal region to 1.5 Å, discover its dimerization, and identify key residues at the dimer interface. Mutations of those interface residues prevent P granule assembly in vivo, de-repress PGL-1 tethered mRNA, and reduce fertility. Therefore, PGL-1 dimerization lies at the heart of both P granule assembly and function. Finally, we identify the P granule-associated Argonaute WAGO-1 as crucial for repression of PGL-1 tethered mRNA. We conclude that P granule function requires both assembly and localized regulators.

Assisted Reproductive Technologies and the Placenta: Clinical, Morphological, and Molecular Outcomes

2018 ◽  
Vol 36 (03/04) ◽  
pp. 240-248 ◽  
Author(s):  
Laren Riesche ◽  
Marisa Bartolomei
Keyword(s):  
Mechanical Stress ◽  
Health Effects ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Epigenetic Reprogramming ◽  
Biological Processes ◽  
Additive Effects ◽  
Growth Development ◽  
And Function

AbstractAs the biological bridge between mother and fetus, the placenta is not only important for the health of the mother and fetus during pregnancy but it also impacts the lifelong health of the fetus. Assisted reproductive technologies (ARTs) involve procedures and exposures that are not characteristic of in vivo reproduction. Moreover, ART procedures occur when the gametes and embryos are undergoing extensive epigenetic reprogramming. Thus, the oxidative, thermal, and mechanical stress that ART procedures introduce can impact the biological processes of placental growth, development, and function with potentially long-lasting health effects for the offspring. Here, we focus on the placenta and summarize the clinical, morphological, and molecular outcomes of ART. This review highlights that ART procedures have additive effects on placental morphology as well as epigenetic disturbances and provides a foundation for reconceptualizing ART outcomes.

scholarly journals Me31B silences translation of oocyte-localizing RNAs through the formation of cytoplasmic RNP complex duringDrosophilaoogenesis

Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3233-3242 ◽  
Author(s):  
Akira Nakamura ◽  
Reiko Amikura ◽  
Kazuko Hanyu ◽  
Satoru Kobayashi
Keyword(s):  
Translational Control ◽  
Rna Localization ◽  
Rna Transport ◽  
Nurse Cells ◽  
Embryonic Patterning ◽  
Maternal Factors ◽  
Dead Box ◽  
Rnp Complex

Embryonic patterning in Drosophila is regulated by maternal factors. Many such factors become localized as mRNAs within the oocyte during oogenesis and are translated in a spatio-temporally regulated manner. These processes are controlled by trans-acting proteins, which bind to the target RNAs to form a ribonucleoprotein (RNP) complex. We report that a DEAD-box protein, Me31B, forms a cytoplasmic RNP complex with oocyte-localizing RNAs and Exuperantia, a protein involved in RNA localization. During early oogenesis, loss of Me31B causes premature translation of oocyte-localizing RNAs within nurse cells, without affecting their transport to the oocyte. These results suggest that Me31B mediates translational silencing of RNAs during their transport to the oocyte. Our data provide evidence that RNA transport and translational control are linked through the assembly of RNP complex.

scholarly journals Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sangmok Kim ◽  
Kelsey C Martin
Keyword(s):  
Motor Neurons ◽  
Synapse Formation ◽  
Synaptic Contact ◽  
Brain Connectivity ◽  
Rna Localization ◽  
Local Translation ◽  
Rna Transport ◽  
Calcium Dependent ◽  
And Function ◽  
Local Stimulation

The persistence of experience-dependent changes in brain connectivity requires RNA localization and protein synthesis. Previous studies have demonstrated a role for local translation in altering the structure and function of synapses during synapse formation and experience-dependent synaptic plasticity. In this study, we ask whether in addition to promoting local translation, local stimulation also triggers directed trafficking of RNAs from nucleus to stimulated synapses. Imaging of RNA localization and translation in cultured Aplysia sensory-motor neurons revealed that RNAs were delivered throughout the arbor of the sensory neuron, but that translation was enriched only at sites of synaptic contact and/or synaptic stimulation. Investigation of the mechanisms that trigger local translation revealed a role for calcium-dependent retrograde netrin-1/DCC receptor signaling. Spatially restricting gene expression by regulating local translation rather than by directing the delivery of mRNAs from nucleus to stimulated synapses maximizes the readiness of the entire neuronal arbor to respond to local cues.

scholarly journals Coordinated genomic control of ciliogenesis and cell movement by RFX2

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Mei-I Chung ◽  
Taejoon Kwon ◽  
Fan Tu ◽  
Eric R Brooks ◽  
Rakhi Gupta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Control Cell ◽  
Cell Movement ◽  
Genomic Analysis ◽  
Apical Surface ◽  
Biological Processes ◽  
Cellular Functions ◽  
Genomic Control ◽  
And Function

The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions.

scholarly journals Maternal mRNAs are regulated by diverse P body–related mRNP granules during early Caenorhabditis elegans development

2008 ◽  
Vol 182 (3) ◽  
pp. 559-572 ◽  
Author(s):  
Scott L. Noble ◽  
Brittany L. Allen ◽  
Lai Kuan Goh ◽  
Kristen Nordick ◽  
Thomas C. Evans
Keyword(s):  
Caenorhabditis Elegans ◽  
Rna Binding ◽  
Germ Line ◽  
Processing Bodies ◽  
Body Protein ◽  
P Bodies ◽  
Granule Morphology ◽  
Maternal Mrnas ◽  
Rnp Granules

Processing bodies (P bodies) are conserved mRNA–protein (mRNP) granules that are thought to be cytoplasmic centers for mRNA repression and degradation. However, their specific functions in vivo remain poorly understood. We find that repressed maternal mRNAs and their regulators localize to P body–like mRNP granules in the Caenorhabditis elegans germ line. Surprisingly, several distinct types of regulated granules form during oocyte and embryo development. 3′ untranslated region elements direct mRNA targeting to one of these granule classes. The P body factor CAR-1/Rap55 promotes association of repressed mRNA with granules and contributes to repression of Notch/glp-1 mRNA. However, CAR-1 controls Notch/glp-1 only during late oogenesis, where it functions with the RNA-binding regulators PUF-5, PUF-6, and PUF-7. The P body protein CGH-1/Rck/Dhh1 differs from CAR-1 in control of granule morphology and promotes mRNP stability in arrested oocytes. Therefore, a system of diverse and regulated RNP granules elicits stage-specific functions that ensure proper mRNA control during early development.

Single-cell profiling of skeletal muscle reveals a novel senolytic target: CRYAB

2021 ◽  
Author(s):  
Chandani Limbad ◽  
Ryosuke Doi ◽  
Julia McGirr ◽  
Serban Ciotlos ◽  
Kevin Perez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Single Cell ◽  
Cellular Senescence ◽  
Cholesterol Biosynthesis ◽  
Cell Types ◽  
New Class ◽  
Single Cell Profiling ◽  
Key Driver ◽  
And Function

Abstract Skeletal muscle mass and function can decline with aging, resulting in a syndrome known as sarcopenia. This decline is linked to functional alterations in critical cell types within mature muscle, including fibro-adipogenic progenitors (FAPs) and satellite cells (SCs), driven in part by cellular senescence. We utilized single-cell RNA sequencing and isolated FAPs and SCs to identify novel targets responsible for senescent cell killing - senolysis. We identified the small alpha-crystalline heat shock protein CRYAB as a novel senolytic target. Using chemical inhibitor screening of CRYAB, we identified 25-hydroxycholesterol (25HC), an endogenous metabolite of cholesterol biosynthesis, as a potent senolytic capable of killing senescent cells. We validated 25HC as a senolytic in mouse and human cells in culture and in vivo in mouse skeletal muscle. Thus, 25HC represents a potential new class of senolytics, which may be useful in combating diseases or physiologies in which cellular senescence is a key driver.

scholarly journals Tyrosine Phosphorylation of Jak2 in the JH2 Domain Inhibits Cytokine Signaling

2004 ◽  
Vol 24 (11) ◽  
pp. 4968-4978 ◽  
Author(s):  
Edward P. Feener ◽  
Felicia Rosario ◽  
Sarah L. Dunn ◽  
Zlatina Stancheva ◽  
Martin G. Myers
Keyword(s):  
Tyrosine Kinases ◽  
Cultured Cells ◽  
Cytokine Signaling ◽  
Biological Processes ◽  
Intact Cells ◽  
Cytokine Stimulation ◽  
And Function ◽  
Jak2 Inhibition ◽  
Dependent Mechanism

ABSTRACT Jak family tyrosine kinases mediate signaling by cytokine receptors to regulate diverse biological processes. Although Jak2 and other Jak kinase family members are phosphorylated on numerous sites during cytokine signaling, the identity and function of most of these sites remains unknown. Using tandem mass spectroscopic analysis of activated Jak2 protein from intact cells, we identified Tyr221 and Tyr570 as novel sites of Jak2 phosphorylation. Phosphorylation of both sites was stimulated by cytokine treatment of cultured cells, and this stimulation required Jak2 kinase activity. While we observed no gross alteration of signaling upon mutation of Tyr221, Tyr570 lies within the inhibitory JH2 domain of Jak2, and mutation of this site (Jak2Y570F) results in constitutive Jak2-dependent signaling in the absence of cytokine stimulation and enhances and prolongs Jak2 activation during cytokine stimulation. Mutation of Tyr570 does not alter the ability of SOCS3 to bind or inhibit Jak2, however. Thus, the phosphorylation of Tyr570 in vivo inhibits Jak2-dependent signaling independently of SOCS3-mediated inhibition. This Tyr570-dependent mechanism of Jak2 inhibition likely represents an important mechanism by which cytokine function is regulated.

scholarly journals Hsa_circ_0000673 is down-regulated in gastric cancer and inhibits the proliferation and invasion of tumor cells by targetting miR-532-5p

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Peng Chang ◽  
Furong Wang ◽  
Yumin Li
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Circular Rnas ◽  
Biological Processes ◽  
Biological Functions ◽  
Mirna Sponge ◽  
New Class ◽  
Non Coding Rnas ◽  
Proliferation And Invasion

Circular RNAs (circRNAs), a new class of endogenous non-coding RNAs, have recently been known to play critical roles in various cellular biological processes, including tumorigenesis, in which they act as an miRNA sponge that regulates gene expression. Thus, revealing the functions of circRNAs in carcinogenesis and cancer development has been of great interest. However, their expression and functions in gastric cancer (GC) development are still largely unknown. Therefore, the present study aimed to identify novel deregulated circRNAs in GC and reveal their biological functions and molecular mechanisms in GC. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression levels of circRNAs in GC tissues, cell lines, and plasma. The MTT assay, colony formation assay, transwell assay, and tumor xenografts in vivo were used to evaluate the effects of circRNAs on the proliferation and invasion of GC. The abovementioned methods coupled with Western blotting were used to investigate the molecular mechanisms. The current study showed that hsa_circ_0000673 was significantly down-regulated in GC. Overexpression of hsa_circ_0000673 inhibited the proliferation and invasion of GC cells. In contrast, hsa_circ_0000673 down-regulation promoted the proliferation and invasion of GC cells. Further studies revealed that hsa_circ_0000673 targetted miR-532-5p and up-regulated the expression of RUNX3. The present study showed that hsa_circ_0000673 was decreased in GC and it exerted tumor-suppressing effects by targetting miR-532-5p and up-regulating RUNX3 expression level. Hsa_circ_0000673 may be a promising diagnosis biomarker and therapeutic target in GC.

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