Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MYCN is an RNA-binding accessory protein of the nuclear exosome

ABSTRACT: The MYCN oncoprotein broadly binds promoters in a heterodimer with its partner protein MAX. MYCN also interacts with the nuclear exosome, a 3’-5’exoribonuclease complex, to facilitate progression through the S phase hinting at an RNA-centric function. Here we show that MYCN forms stable high molecular weight complexes with multiple RNA-binding proteins including the nuclear exosome. RNA-binding assays reveal that MYCN directly binds to thousands of predominantly intronic RNA sites via a short, highly conserved sequence motif termed MYCBoxI. Exosome depletion results in MYCN globally re-localizing from promoters to intronic RNAs. The vacant promoters are then occupied by the MXD transcription repressor protein MNT, which inhibits MYCN-dependent transcription. MYCN fosters the degradation of its bound introns via tight association with the nuclear exosome targeting complex (NEXT). Our data demonstrate that MYCN is an RNA-binding protein that controls RNA turnover and argue that the competition between MYCN’s RNA- and DNA-bound states links the dynamics of the MYCN/MAX/MXD network to mRNA processing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240764 | GEO | 2024/06/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The MYCN oncoprotein is an RNA-binding protein that promotes nascent RNA turnover via the NEXT targeting complex of the nuclear exosome

Project description:The MYCN oncoprotein forms a DNA-binding heterodimer with its partner protein MAX. MYCN-driven tumor cells depend on the nuclear exosome, a 3`-5` RNA exonuclease complex, to progress through S phase. Here we show that MYCN forms stable high molecular weight complexes with the nuclear exosome and additional RNA-binding proteins. Enhanced cross-linking and immunoprecipitation (eCLIP) experiments reveal that MYCN binds to thousands of sites on RNA, mainly localized in introns. MYCN directly binds RNA with a preference for UG-rich sequences via a short, highly conserved sequence motif termed MycBox I. Upon exosome inhibition, MYCN relocalizes globally from promoters to intronic RNAs; at promoters, MYCN is then replaced by the repressive MXD6 (MNT) protein, leading to the recruitment of histone deacetylase complexes and inhibition of MYCN-dependent transcription. MYCN is tightly associated with the exosome targeting complex NEXT and promotes the degradation of non-polyadenylated RNA at its bound introns. Our data demonstrate that MYCN is an RNA-binding protein that controls nascent RNA turnover and argue that the competition between RNA- and DNA-bound states of MYCN links the dynamics of the MYCN/MAX/MXD network to the completion of mRNA processing.

2024-07-18 | PXD044446 | Pride

MYCN is an RNA-binding accessory protein of the nuclear exosome

Project description:MYCN is an RNA-binding accessory protein of the nuclear exosome

| PRJNA1005212 | ENA

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [expression array]

Project description:Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome, however, the way they are recognized and targeted to the exosome is not fully understood. The recently identified Schizosaccharomyces pombe MTREC complex has been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs. Here, we report that the MTREC complex is also the major nuclear exosome targeting complex for CUTs and unspliced mRNAs. MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and -processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of aberrant, cryptic transcripts. Genome-wide expression analysis of MTREC, Nuclear Exosome, TRAMP, Nrd complex members All experiments were performed twice in biological replicates, except that rmn1Δ and mmi1Δ mei4-P572 were perfomed once.

2015-05-22 | E-GEOD-64979 | biostudies-arrayexpress

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [RIP-ChIP]

Project description:Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome, however, the way they are recognized and targeted to the exosome is not fully understood. The recently identified Schizosaccharomyces pombe MTREC complex has been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs. Here, we report that the MTREC complex is also the major nuclear exosome targeting complex for CUTs and unspliced mRNAs. MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and -processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of aberrant, cryptic transcripts. All experiments were performed twice in biological replicates.

2015-05-22 | E-GEOD-64980 | biostudies-arrayexpress

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [RNA-Seq]

Project description:Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome, however, the way they are recognized and targeted to the exosome is not fully understood. The recently identified Schizosaccharomyces pombe MTREC complex has been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs. Here, we report that the MTREC complex is also the major nuclear exosome targeting complex for CUTs and unspliced mRNAs. MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and -processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of aberrant, cryptic transcripts. RNA sequencing of WT and mutant S.pombe strains, processed data is normalized to median non-intron containing gene-expression, no replicates

2015-05-22 | E-GEOD-64991 | biostudies-arrayexpress

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome

Project description:Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here, we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is also the major nuclear exosome targeting complex for CUTs and unspliced pre-mRNAs in Schizosaccharomyces pombe. MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and -processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of CUTs.

2015-04-22 | PXD001908 | Pride

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [expression array]

2015-05-22 | GSE64979 | GEO

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [RNA-Seq]

2015-05-22 | GSE64991 | GEO

The fission yeast MTREC complex targets CUTs and unspliced mRNAs to the nuclear exosome [RIP-ChIP]

2015-05-22 | GSE64980 | GEO

The MYCN oncoprotein resolves conflicts of stalling RNA Polymerase with the replication fork [DP_EXOSC10_Screen]

Project description:During the S-phase, conflicts of replication forks with RNA Polymerase II (RNAPII) threaten genomic stability. While the PAF complex can resolve such conflicts during elongation, the particularly deleterious conflicts with stalling RNAPII are resolved by an as of yet unknown mechanism. Here we show that the MYCN oncoprotein forms a ternary complex with RNAPII and the nuclear RNA exosome, a 3’‑5’ exoribonuclease complex. Together with TFIIS, this complex restarts promoter‑proximal RNAPII, allows escape from co-directional transcription-replication conflicts and prevents double‑strand break accumulation. In cells lacking RNA exosome function, MYCN globally terminates transcription. MYCN-mediated termination is triggered by ATM‑dependent recruitment of BRCA1, which then stabilizes nuclear mRNA decapping complexes. Disruption of mRNA decapping activates ATR, indicative of head-on transcription-replication conflicts, and inhibits DNA replication. We propose that MYCN resolves transcription-replication conflicts via this two-step mechanism to sustain the rapid proliferation of neuroendocrine tumor cells.

2021-12-10 | GSE164568 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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