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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE61073 | GEO | 2014/09/25

SECONDARY ACCESSION(S): PRJNA260185

REPOSITORIES: GEO

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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. Refer to individual Series

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

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.

2014-09-25 | GSE60976 | 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 (sequencing)

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

| PRJNA258219 | ENA

Mammalian microRNAs predominantly act to decrease target mRNA levels.

Project description:MicroRNAs (miRNAs) are endogenous approximately 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.

| S-EPMC2990499 | biostudies-literature

Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins

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

2014-07-16 | E-GEOD-49649 | biostudies-arrayexpress

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

SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay.

Project description:In mammals, nonsense-mediated mRNA decay (NMD) functions in post-transcriptional gene regulation as well as mRNA surveillance. A key NMD factor, Upf1, becomes hyperphosphorylated by SMG1 kinase during the recognition of NMD substrates. Hyperphosphorylated Upf1 interacts with several factors including SMG5, SMG6, SMG7 and PNRC2 to trigger rapid mRNA degradation. However, the possible cross-talk among these factors and their selective use during NMD remain unknown. Here, we show that PNRC2 is preferentially complexed with SMG5, but not with SMG6 or SMG7, and that downregulation of PNRC2 abolishes the interaction between SMG5 and Dcp1a, a component of the decapping complex. In addition, tethering experiments reveal the function of Upf1, SMG5 and PNRC2 at the same step of NMD and the requirement of SMG6 for Upf1 for efficient mRNA degradation. Intriguingly, microarray results reveal the significant overlap of SMG5-dependent NMD substrates more with PNRC2-dependent NMD substrates than with SMG7-dependent NMD substrates, suggesting the functional dominance of SMG5-PNRC2, rather than SMG5-SMG7, under normal conditions. The results provide evidence that, to some extent, endogenous NMD substrates have their own binding preference for Upf1-interacting adaptors or effectors.

| S-EPMC3553988 | biostudies-literature

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