Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A biogenesis step upstream of Microprocessor controls miR-17~92 expression

ABSTRACT: The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell differentiation. We identify a new miRNA biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA), that is an efficient substrate for Microprocessor. An autoinhibitory 5’ RNA fragment is cleaved to generate pro-miRNA and selectively license Microprocessor-mediated production of pre-miR-17, -18a, -19a, 20a, and -19b. Using genetic, biochemical, and structural methods we define two complementary cis-regulatory repression domains required for the formation of this inhibitory RNA conformation. We find the endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are required for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated generation of pro-miRNA explains the posttranscriptional control of miR-17~92 expression in development. Illumina RNAseq in WT, dgcr8-/- and dicer-/- mESCs and small RNA seq in WT mESCs

ORGANISM(S): Mus musculus

SUBMITTER: Peng Du

PROVIDER: E-GEOD-68699 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

A biogenesis step upstream of Microprocessor controls miR-17~92 expression

Project description:The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell differentiation. We identify a new miRNA biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA), that is an efficient substrate for Microprocessor. An autoinhibitory 5’ RNA fragment is cleaved to generate pro-miRNA and selectively license Microprocessor-mediated production of pre-miR-17, -18a, -19a, 20a, and -19b. Using genetic, biochemical, and structural methods we define two complementary cis-regulatory repression domains required for the formation of this inhibitory RNA conformation. We find the endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are required for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated generation of pro-miRNA explains the posttranscriptional control of miR-17~92 expression in development.

2015-05-11 | GSE68699 | GEO

Oncogenic biogenesis of pri-miR-17~92

Project description:The microRNAs encoded by the miR-17~92 polycistron are commonly overexpressed in cancer and orchestrate a wide range of oncogenic functions. Here, we identify a novel mechanism for miR-17~92 oncogenic function through the disruption of endogenous miRNA processing. We show that upon oncogenic overexpression of the miR-17~92 primary transcript (pri-miR-17~92), the Microprocessor complex remains associated with partially processed intermediates that aberrantly accumulate. These intermediates reflect a series of hierarchical and conserved steps in the early processing of the pri-miR-17~92 transcript. Encumbrance of the Microprocessor by miR-17~92 intermediates leads to the broad, but selective, downregulation of co-expressed polycistronic miRNAs, including miRNAs derived from tumour suppressive miR-34b/c, and from the Dlk1-Dio3 polycistrons. We propose that the newly identified steps of polycistronic miR-17~92 biogenesis contribute to the oncogenic re-wiring of gene regulation networks. Our results reveal new functional paradigms for polycistronic miRNAs in cancer.

2019-05-20 | GSE130282 | GEO

Endogenous shRNAs, siRNAs, and Other Microprocessor-independent, Dicer-dependent Small RNAs in Mouse ES Cells

Project description:Canonical microRNAs (miRNAs) require two processing steps: the first by the Microprocessor, a complex of DGCR8 and Drosha, and the second by Dicer. dgcr8delta/delta mouse embryonic stem cells (mESCs) have less severe phenotypes than dicer1delta/delta mESCs, suggesting a physiological role for Microprocessor-independent, Dicer-dependent small RNAs. To identify these small RNAs with unusual biogenesis, we performed high-throughput sequencing from wild type, dgcr8delta/delta, and dicer1delta/delta mESCs. Several of the DGCR8-independent, Dicer-dependent RNAs were non-canonical miRNAs. These derived from mirtrons and a newly identified subclass of miRNA precursors, which appears to be the endogenous counterpart of short hairpin RNAs (shRNAs). Our analyses also revealed endogenous siRNAs resulting from Dicer cleavage of long hairpins, the vast majority of which originated from one genomic locus with tandem, inverted short interspersed nuclear elements (SINEs). Our results extend the known diversity of mammalian small-RNA generating pathways and show that mammalian siRNAs exist in tissues outside of oocytes. Small RNAs were sequenced from wt, dgcr8(-), and dicer(-) mouse ES cells and the frequencies of small RNA types compared between the three. This record includes Illumina-platform-generated datasets from all three samples and 454-platform-generated datasets from wt and dgcr8(-) samples. [raw data files are unavailable]

2008-09-09 | E-GEOD-12521 | biostudies-arrayexpress

XPO5 is required for miRNA biogenesis and promotes primary miRNA processing independent of RanGTP

Project description:XPO5 mediates nuclear export of miRNA hairpin precursors in a RanGTP-dependent manner. However, the requirement of XPO5 for global miRNA biogenesis and mammalian development and XPO5-associated RNA species are not determined. Here we show that XPO5 is required for mouse embryonic development and morphogenesis of skin and brain. Loss of XPO5 compromises the biogenesis of most miRNAs and that leads to severe developmental defects. Surprisingly, XPO5 not only associates with miRNA hairpin precursors but also pervasively binds to double-stranded RNA (dsRNA) regions found in many cellular RNAs and some clustered pri-miRNAs. The binding of XPO5 to miR-17~92 pri-miRNAs is RanGTP-independent. Pre-incubation with XPO5 enhances the processing efficiency of the DROSHA/DGCR8 microprocessor. Together, our studies demonstrate the requirement of XPO5 for miRNA biogenesis and mouse development, reveal an unexpected role of XPO5 for recognizing and facilitating the nuclear cleavage of clustered pri-miRNAs and identify numerous cellular RNAs as novel XPO5 subtracts.

2020-02-19 | GSE111964 | GEO

Mus musculus

Project description:A biogenesis step upstream of Microprocessor controls miR-17~92 expression

| PRJNA283413 | ENA

miRNA expression in E18.5 murine total lung tissue

Project description:Knockout of the ubiquitously expressed microRNA-17~92 cluster in mice produces a lethal developmental lung defect. We validated the equally widely expressed pro-apoptotic Bim gene as joint target of miR-17~92 cluster members. To study the contribution of miR-17~92:Bim interaction to miR-17~92 overall function, we set up a system of conditional mutagenesis of the Bim 3’UTR. Blocking miR-17~92:Bim interaction early in development phenocopied the lethal lung phenotype of miR-17~92 ablation. Thus, despite hundreds of overall predicted targets vital miRNA functions can be mediated by a single target gene.

2019-11-10 | GSE123671 | GEO

Control of oligodendroglial cell number by the miR-17~92 family of miRNA cluster (miRNA Exiqon Part)

Project description:The generation of myelinating cells in the central nervous system (CNS) requires the initiation of specific gene-expression programs in oligodendrocytes. We reasoned that miRNAs could play an important role in this process by regulating critical developmental genes. Microarray profiling of cultured oligodendrocytes identifies the miR-17~92 family of miRNA cluster as highly enriched miRNAs in oligodendrocytes.We specifically deleted the miR-17~92 cluster in oligodendrocytes using the 2´3´-cyclic nucleotide 3´-phosphodiesterase (CNP)-Cre mice. Absence of miR-17~92 leads to a reduction of oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocytes promotes cell proliferation by influencing Akt signalling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17~92 cluster is crucial in this process.

2010-06-01 | GSE21799 | GEO

Control of oligodendroglial cell number by the miR-17~92 family of miRNA cluster (miRNA Agilent Part)

Project description:The generation of myelinating cells in the central nervous system (CNS) requires the initiation of specific gene-expression programs in oligodendrocytes. We reasoned that miRNAs could play an important role in this process by regulating critical developmental genes. Microarray profiling of cultured oligodendrocytes identifies the miR-17~92 family of miRNA cluster as highly enriched miRNAs in oligodendrocytes. We specifically deleted the miR-17~92 cluster in oligodendrocytes using the 2´3´-cyclic nucleotide 3´-phosphodiesterase (CNP)-Cre mice. Absence of miR-17~92 leads to a reduction of oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocytes promotes cell proliferation by influencing Akt signalling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17~92 cluster is crucial in this process.

2010-06-01 | GSE21798 | GEO

Control of oligodendroglial cell number by the miR-17~92 family of miRNA cluster (mRNA profiling)

2010-06-01 | GSE21797 | GEO

Two miRNAs are sufficient for C. elegans embryogenesis

Project description:The Microprocessor, composed of Drosha and Pasha/DGCR8, is necessary for the biogenesis of canonical microRNAs (miRNAs), and required for animal embryogenesis. However, the cause for this requirement is largely unknown. The Microprocessor may be required to produce one or few essential miRNAs, or alternatively, many individually non-essential miRNAs. Additionally, Drosha and Pasha/DGCR8 may be required for processing non-miRNA substrates. To distinguish between these possibilities, we developed a system in C. elegans to stringently deplete embryos from the Microprocessor and miRNAs. We show that the early embryonic arrest upon loss of the Microprocessor is rescued by the addition of two individual miRNAs from the miR-35 and miR-51 families, resulting in morphologically normal larvae. Thus, just two canonical miRNAs are sufficient for morphogenesis and organogenesis in C. elegans, and indicate that miRNA processing explains the essential requirement for the Microprocessor during embryogenesis.

2020-11-21 | GSE153233 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data