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MRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (sequencing)

ABSTRACT: mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (sequencing)

OTHER RELATED OMICS DATASETS IN: GSE60426

PROVIDER: PRJNA258219 | ENA |

REPOSITORIES: ENA

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mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (sequencing)

Project description:MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%–>90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.

2014-09-25 | GSE60426 | GEO

mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (gene expression)

Project description:MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to many additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition or translational state, mRNA destabilization explains most (70% to >90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect on gene expression is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results add to the fundamental understanding of miRNAs, imply that consequential miRNA-mediated repression is largely irreversible and simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects. 6 samples from a variety of primary cell types

2014-09-25 | E-GEOD-60976 | biostudies-arrayexpress

mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (gene expression)

Project description:MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to many additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition or translational state, mRNA destabilization explains most (70% to >90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect on gene expression is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results add to the fundamental understanding of miRNAs, imply that consequential miRNA-mediated repression is largely irreversible and simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.

2014-09-25 | GSE60976 | GEO

mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues.

Project description:MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%->90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.

| S-EPMC4292926 | biostudies-literature

mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-09-25 | GSE61073 | GEO

mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-09-25 | E-GEOD-61073 | biostudies-arrayexpress

Project description:mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues

| PRJNA260185 | ENA

Destabilization of AETFC through C/EBPalpha-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation

Project description:In t(8;21) leukemic cells, the leukemogenic fusion protein AML1-ETO is stabilized and functions through the AML1-ETO-containing transcription factor complex (AETFC). Destabilization of AETFC thus provides a strategy to target AML1-ETO. In this study, we found that AETFC can be destabilized by a specific mechanism involving a direct repression of the core component LYL1 by C/EBPalpha at transcriptional level. We performed a ChIP-seq analysis of the genome-wide occupancy of C/EBPalpha and identifeid a -1 kb C/EBPalpha-binding site in the LYL1 locus that mediate this repression. As LYL1 acts as a linker between the AML1-ETO-E and LMO2-LDB1 parts of AETFC, depletion of LYL1 causes a destabilization of AETFC, which increases susceptibility of the leukemic cells to differentiation. Our results have provided a novel mechanism by which C/EBPalpha can directly destabilize AETFC, and have identified LYL1 as a new therapeutic target for treatment of t(8;21) leukemia.

2019-02-19 | GSE114642 | GEO

Mus musculus

Project description:mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues (gene expression)

| PRJNA260030 | ENA

Mammalian microRNAs predominantly act to decrease target mRNA levels

Project description:MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output. This SuperSeries is composed of the SubSeries listed below.

2010-08-03 | GSE22004 | GEO

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