Ontology highlight
ABSTRACT:
PROVIDER: PRJNA121289 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The road from transcription to protein synthesis is paved with many obstacles, allowing for several modes of post-transcriptional regulation of gene expression. A fundamental player in mRNA biology, DDX3X is an RNA binding protein that regulates mRNA translation. By monitoring dynamics of mRNA abundance and translation following DDX3X depletion, we observe stabilization of translationally suppressed mRNA. We used interpretable statistical learning models to uncover GC content in the coding sequence as the major feature underlying RNA stabilization. GC content-related mRNA regulation is detectable in other studies, including hundreds of ENCODE datasets and recent work focusing on mRNA dynamics in the cell cycle. We provide further evidence for mRNA stabilization by detailed analysis of RNA-seq profiles in hundreds of samples, including a recently published Ddx3x conditional mouse model exhibiting cell cycle and neurogenesis defects. Our study identifies a ubiquitous feature underlying mRNA regulation and highlights the importance of quantifying multiple steps of the gene expression cascade, where RNA abundance and protein production are often uncoupled.
2023-08-08 | GSE218433 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112765 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112764 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112763 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112762 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112761 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112760 | GEO
Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.
2018-07-25 | GSE112766 | GEO
Project description:This the model from the article:
A quantitative model for mRNA translation in Saccharomyces cerevisiae.
You T, Coghill GM, Brown AJ. Yeast.
2010 Mar 19. epub ahead of print, PMID: 20306461
, doi: 10.1002/yea.1770
Abstract:
Messenger RNA (mRNA) translation is an essential step in eukaryotic gene expression that contributes to the regulation of this process. We describe a deterministic model based on ordinary differential equations that describe mRNA translation in Saccharomyces cerevisiae. This model, which was parameterized using published data, was developed to examine the kinetic behaviour of translation initiation factors in response to amino acid availability. The model predicts that the abundance of the eIF1-eIF3-eIF5 complex increases under amino acid starvation conditions, suggesting a possible auxiliary role for these factors in modulating translation initiation in addition to the known mechanisms involving eIF2. Our analyses of the robustness of the mRNA translation model suggest that individual cells within a randomly generated population are sensitive to external perturbations (such as changes in amino acid availability) through Gcn2 signalling. However, the model predicts that individual cells exhibit robustness against internal perturbations (such as changes in the abundance of translation initiation factors and kinetic parameters). Gcn2 appears to enhance this robustness within the system. These findings suggest a trade-off between the robustness and performance of this biological network. The model also predicts that individual cells exhibit considerable heterogeneity with respect to their absolute translation rates, due to random internal perturbations. Therefore, averaging the kinetic behaviour of cell populations probably obscures the dynamic robustness of individual cells. This highlights the importance of single-cell measurements for evaluating network properties. Copyright (c) 2010 John Wiley and Sons, Ltd.
This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL8459127548 | BioModels
Project description:Schmitz2014 - RNA triplex formation
The model is parameterized using the
parameters for gene CCDC3 from Supplementary Table S1. The two
miRNAs which form the triplex together with CCDC3 are miR-551b and
miR-138.
This model is described in the article:
Cooperative gene regulation
by microRNA pairs and their identification using a
computational workflow.
Schmitz U, Lai X, Winter F,
Wolkenhauer O, Vera J, Gupta SK.
Nucleic Acids Res. 2014 Jul; 42(12):
7539-7552
Abstract:
MicroRNAs (miRNAs) are an integral part of gene regulation
at the post-transcriptional level. Recently, it has been shown
that pairs of miRNAs can repress the translation of a target
mRNA in a cooperative manner, which leads to an enhanced
effectiveness and specificity in target repression. However, it
remains unclear which miRNA pairs can synergize and which genes
are target of cooperative miRNA regulation. In this paper, we
present a computational workflow for the prediction and
analysis of cooperating miRNAs and their mutual target genes,
which we refer to as RNA triplexes. The workflow integrates
methods of miRNA target prediction; triplex structure analysis;
molecular dynamics simulations and mathematical modeling for a
reliable prediction of functional RNA triplexes and target
repression efficiency. In a case study we analyzed the human
genome and identified several thousand targets of cooperative
gene regulation. Our results suggest that miRNA cooperativity
is a frequent mechanism for an enhanced target repression by
pairs of miRNAs facilitating distinctive and fine-tuned target
gene expression patterns. Human RNA triplexes predicted and
characterized in this study are organized in a web resource at
www.sbi.uni-rostock.de/triplexrna/.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000530.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000530 | BioModels