Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (RNA-Seq)

ABSTRACT: Nuclear RNA decay has emerged as a mechanism for post-transcriptional gene regulation in cultured cells. However, whether this actually occurs in animals and is biologically relevant remains largely unexplored. Here, we demonstrate that MTR4, a central cofactor of the nuclear RNA exosome complex, is required for embryogenesis and spermatogenesis. Embryonic development of MTR4 knockout mice arrests at 6.5 days. Specific knock out of MTR4 in mouse advanced germ cells results in male infertility with a severe defect in meiotic initiation, with pre-meiotic germ cells accumulating a dysregulated transcriptome with mixed features of mitosis and meiosis. Interestingly, MTR4 pervasively binds to various types of RNAs but selectively degrades those exhibiting specific binding patterns. Moreover, polyadenylated retrotransposon RNAs are removed by the nuclear exosome, preventing their negative impacts on gene expression and potential mutagenic threat. Our work underscores the importance of nuclear RNA decay in regulating germline transcripts to ensure a gene expression program for the mitotic-to-meiotic transition.

ORGANISM(S): Mus musculus

PROVIDER: GSE253154 | GEO | 2025/02/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (LACE-Seq)

Project description:Nuclear RNA decay has emerged as a mechanism for post-transcriptional gene regulation in cultured cells. However, whether this actually occurs in animals and is biologically relevant remains largely unexplored. Here, we demonstrate that MTR4, a central cofactor of the nuclear RNA exosome complex, is required for embryogenesis and spermatogenesis. Embryonic development of MTR4 knockout mice arrests at 6.5 days. Specific knock out of MTR4 in mouse advanced germ cells results in male infertility with a severe defect in meiotic initiation, with pre-meiotic germ cells accumulating a dysregulated transcriptome with mixed features of mitosis and meiosis. Interestingly, MTR4 pervasively binds to various types of RNAs but selectively degrades those exhibiting specific binding patterns. Moreover, polyadenylated retrotransposon RNAs are removed by the nuclear exosome, preventing their negative impacts on gene expression and potential mutagenic threat. Our work underscores the importance of nuclear RNA decay in regulating germline transcripts to ensure a gene expression program for the mitotic-to-meiotic transition.

2025-02-23 | GSE253156 | GEO

MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus

Project description:Recent in vitro reconstitution analyses have proven that the physical interaction between the exosome core and MTR4 helicase, which promotes the exosome activity, is maintained by either MPP6 or RRP6. However, knowledge regarding the function of MPP6 with respect to in vivo exosome activity remains scarce. Here we demonstrate a facilitative function of MPP6 that composes a specific part of MTR4-dependent substrate decay by the human exosome. Using RNA polymerase II-transcribed poly(A)+ substrate accumulation as an indicator of a perturbed exosome, we found functional redundancy between RRP6 and MPP6 in the decay of these poly(A)+ transcripts. MTR4 binding to the exosome core via MPP6 was essential for MPP6 to exert its redundancy with RRP6. However, at least for the decay of our identified exosome substrates, MTR4 recruitment by MPP6 was not functionally equivalent to recruitment by RRP6. Genome-wide classification of substrates based on their sensitivity to each exosome component revealed that MPP6 deals with a specific range of substrates, and highlights the importance of MTR4 for their decay. Considering recent findings of competitive binding to the exosome between auxiliary complexes, our results suggest that the MPP6-incorporated MTR4-exosome complex is one of multiple alternative complexes rather than the prevailing one.

2022-06-19 | GSE184274 | GEO

Hydrogen-deuterium exchange mass spectrometry of wt Mtr4 with various RNA substrates

Project description:Mtr4 is a eukaryotic RNA helicase required for RNA decay by the nuclear exosome. Previous studies have shown how RNA enroute to the exosome threads through the highly conserved helicase core of Mtr4. Mtr4 also contains an arch domain, although details of potential interactions between the arch and RNA have been elusive. To understand the interaction of Saccharomyces cerevisiae Mtr4 with various RNAs, we have characterized RNA binding in solution using hydrogen-deuterium exchange mass spectrometry, and affinity and unwinding assays. We have identified RNA interactions within the helicase core that are consistent with existing structures and do not vary between tRNA, single-stranded RNA, and double-stranded RNA constructs. We have also identified novel RNA interactions with a region of the arch known as the fist or KOW. These interactions are important for RNA unwinding and vary in strength depending on RNA structure and length. They account for Mtr4 discrimination between different RNAs. These interactions further drive Mtr4 to adopt a closed conformation characterized by reduced dynamics of the arch arm and intra-domain contacts between the fist and helicase core.

2022-03-07 | PXD031962 | Pride

Rip-seq of MTR4 in PLC/PRF5

Project description:Metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis by providing cancer cells with energy and substrates of biosynthesis, and also plays a key role in inducing immune suppressive tumor microenvironment that inhibits tumor immunotherapy. Therefore, to develop more effective cancer therapy, it is important to elucidate mechanisms that control cancer metabolic switch. MTR4 is a RNA helicase associated with nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrated that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and this predicts poor prognosis of HCC patients. MTR4 is required for HCC tumorigenesis by maintaining cancer metabolic switch. Mechanistically, MTR4 is required for the expression of critical glycolytic proteins such as GLUT1 and PKM2 by binding to their pre-mRNA and ensuring correct alternative splicing. c-Myc binds to the promoter of MTR4 gene and is required for MTR4 expression, indicating that MTR4 is a key mediator of c-Myc function in promoting cancer metabolism. These findings reveal an important pathway to drive cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.

2019-12-19 | GSE129261 | GEO

An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

Project description:Many long noncoding RNAs (lncRNAs) are unstable and rapidly degraded in the nucleus by the nuclear exosome. An exosome adaptor complex called NEXT (nuclear exosome targeting) functions to facilitate turnover of some of these lncRNAs. Here we show that knockdown of one NEXT subunit, Mtr4, but neither of the other two subunits, resulted in accumulation of two types of lncRNAs: prematurely terminated RNAs (ptRNAs) and upstream antisense RNAs (uaRNAs). This suggested a NEXT-independent Mtr4 function, and, consistent with this, we isolated a distinct complex containing Mtr4 and the zinc finger protein ZFC3H1. Strikingly, knockdown of either protein not only increased pt/uaRNA levels but also led to their accumulation in the cytoplasm. Furthermore, all pt/uaRNAs examined associated with active ribosomes, but, paradoxically, this correlated with a global reduction in heavy polysomes and overall repression of translation. Our findings highlight a critical role for Mtr4/ZFC3H1 in nuclear surveillance of naturally unstable lncRNAs to prevent their accumulation, transport to the cytoplasm, and resultant disruption of protein synthesis.

2017-08-22 | GSE102893 | GEO

The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (LACE-Seq)

Project description:The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (LACE-Seq)

| PRJNA1064128 | ENA

The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (RNA-Seq)

Project description:The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation (RNA-Seq)

| PRJNA1064125 | ENA

Xrn1-sensitive lncRNAs accumulate upon inactivation of Dbp2 and Mtr4

Project description:To investigate the role of the helicases Dbp2 and Mtr4 in the decay of Xrn1-sensitive lncRNAs, we performed RNA-Seq in yeast cells lacking Dbp2 or depleted for Mtr4.

2023-07-27 | GSE235552 | GEO

NRDE2 negatively regulates nuclear exosome functions

Project description:The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.

2019-03-14 | GSE120206 | GEO

Structural basis for RNA capture and surveillance by the human Nuclear Exosome Targeting (NEXT) complex

Project description:Abstract: RNA quality control relies on co-factors and adaptors to identify and prepare substrates for degradation by ribonucleases such as the 3′ to 5′ ribonucleolytic RNA exosome. Here, we determined cryo-electron microscopy structures of human Nuclear Exosome Targeting (NEXT) complexes bound to RNA, that reveal mechanistic insights to substrate recognition and early steps that precede RNA handover to the exosome. The structures illuminate ZCCHC8 as a scaffold, mediating homodimerization while embracing the MTR4 helicase and flexibly anchoring RBM7 to the helicase core. All three subunits collaborate to bind the RNA, with RBM7 and ZCCHC8 engaging sequences upstream of the 3′ end that is bound by MTR4. ZCCHC8 obscures MTR4 surfaces that are important for RNA binding and extrusion as well as surfaces important for MPP6-dependent recruitment and docking onto the RNA exosome core, features of which might contribute to coordinating RNA translocation and extrusion from the helicase to exosome recruitment and decay.

2022-06-09 | GSE185374 | 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