Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex
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PROVIDER: PRJNA591581 | ENA |
REPOSITORIES: ENA
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Project description:Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3’-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.
2021-05-01 | GSE140931 | GEO
Project description:Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3'-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.
| S-EPMC8249388 | biostudies-literature
Project description:Structural birth defects are the leading cause of infant mortality in the United States. Many of these defects are associated with abnormal anatomical left-right asymmetry. Despite the importance of orienting organs along the left-right (L-R) axis during development, very little is known about the molecular events that control this process. To elucidate the genetic mechanisms that shape the L-R asymmetry of individual organs, we sought to identify genes that are expressed in L-R asymmetric patterns during organ development. To accomplish this goal, we took advantage of the exceptionally large Budgett’s frog (Lepidobatrachus laevis) embryo to profile gene expression by RNA-seq in the left versus right halves of the developing stomach. Using this data, we have constructed a de novo Lepidobatrachus transcriptome and identified ~26,000 unique transcripts with human homology based on reciprocal BLAST analyses. Over 300 transcripts were L-R asymmetrically expressed within the stomach. Among these candidates are some of the few genes already known to play a role in L-R asymmetric development, validating our strategy for L-R gene discovery.
2023-05-26 | GSE99817 | GEO
Project description:Colonic Crohn's left and right colon
| PRJNA593867 | ENA
Project description:The Ccr4-Not complex is a major regulator of stress responses that controls gene expression at multiple levels, from transcription to mRNA decay. Ccr4, a core subunit of the complex, is the main cytoplasmic deadenylase in Saccharomyces cerevisiae, however its mRNA targets have not been mapped on a genome-wide scale. Here we describe a genome-wide approach, RNA immunoprecipitation-high throughput sequencing (RIP-seq), to identify the RNAs bound to Ccr4, and two proteins that associate with it, Dhh1 and Puf5. All three proteins were preferentially bound to lowly abundant mRNAs, most often at the 3’ end of the transcript. Furthermore, Ccr4, Dhh1 and Puf5 are recruited to mRNAs that are targeted by other RNA-binding proteins that promote decay, mRNA transport and inhibit translation. Although Ccr4-Not regulates mRNA transcription and decay, Ccr4 recruitment to mRNAs correlates better with decay rates, suggesting it imparts greater control over transcript abundance through decay. Ccr4-enriched mRNAs are refractory to control by the other deadenylase complex in yeast, Pan2/3, suggesting a division of labor between these deadenylation complexes. Finally, Ccr4 and Dhh1 associate with mRNAs whose abundance increases during nutrient starvation and those that fluctuate during metabolic and oxygen consumption cycles, which explains the known genetic connections between these factors and nutrient utilization and stress pathways.
2017-12-04 | GSE72366 | GEO
Project description:Wild type, ccr4∆, ccr4∆ pbp1∆ cells were grown in YPD medium from log phase to stationary phase. Total RNAs ere extracted and subjected to microarray analysis.
2022-03-18 | GSE198743 | GEO
Project description:Left and right heart ventricles of adult male mice were profiled to determine the differences in gene expression, control, coordination and signaling fabrics Two-sides (L= left, R = right) gene expression profiling experiment in adult mouse male (M) ventricles (V). 4 biological replicates: MVL1-4, MVR1-4.
2013-03-21 | E-GEOD-45348 | biostudies-arrayexpress
Project description:Left and Right phrenic nerves, which innervate the left and right diaphragm muscles, exhibit different innervation patterns. This left/right (L/R) asymmetry is established at the onset of innervation by a developmental program that requires Nodal. Phenotype analysis suggests that the cervical motoneurons, which innervate the diaphragm, have a L/R imprint that contributes to set the L/R asymmetries of innervation. We used microarray to analyze the expression profile of left and right cervical motoneurons before diaphragm innervation
2017-06-08 | GSE84778 | GEO
Project description:A comparison of human cardiac gene expression profile in paired samples of right atrium and left ventricle extracted in vivo<br><br>
2012-01-30 | E-MEXP-3396 | biostudies-arrayexpress
Project description:The transmission of the malaria parasite between mosquitoes and mammals requires translational repression to ensure that only the proper proteins are expressed at the right time, while still allowing the parasite to prepare the mRNAs it will need for the next developmental stage. With relatively few known specific transcription factors (ApiAP2 family) that may specifically initiate gene transcription, Plasmodium parasites also regulate the stability and turnover of transcripts to provide more comprehensive gene regulation. The CAF1/CCR4/NOT complex has been shown in model organisms to be important for not only mRNA degradation, but also translational control through its deadenylases CAF1 and CCR4. However, few proteins that impose translational repression in Plasmodium sexual stages are known, and those that are characterized primarily affect female gametocytes. Therefore, we have characterized two deadenylases and have uncovered their roles in transmission. We have identified and characterized CCR4-1, which we show plays a role in activating male gametocytes, stabilizing transcripts in gametocytes, and regulating host-to-vector transmission. We find that when ccr4-1 is genetically deleted, there is a loss in the coordination of male gametocyte activation and a reduction in the ability of the parasite to productively infect the mosquito, which is independent of its effect upon male activation. Comparative RNA-seq shows that the deletion of ccr4-1 affects many transcripts that are translationally repressed in females, are related to male gamete function, and/or are important for early mosquito stage development. In contrast, we found that genetic deletion of the major deadenylase Caf1 is lethal. However, we observed that expression of only the N-terminal Caf1 domain is permissive, yet prevents proper complex assembly and phenocopies the ccr4-1 deletion. We therefore conclude that the general and transmission-specialized deadenylases of the CAF1/CCR4/NOT complex play critical and intertwined roles in parasite growth and transmission.
2019-01-02 | GSE101484 | GEO