hnRNP M interacts with PSF and p54nrb and co-localizes within defined nuclear structures

Marko, Marija; Leichter, Michael; Patrinou-Georgoula, Meropi; Guialis, Apostolia

doi:10.1016/j.yexcr.2009.10.021

Cited by 49 publications

(40 citation statements)

References 38 publications

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“…The corresponding proteins all contribute to paraspeckle structures that are presumed to play a role in mRNA retention in the nucleus. 31, 32 As these rapid and distinct regulations had not been expected by us, we used a different, but mechanistically related, damage model for confirmation: the cells were exposed to the complex I inhibitor rotenone (100 nM) and very similar transcriptional changes were observed (Supplementary Figure S7). Thus, the transcriptome response we observed for MPP + may reflect a general response to mitochondrial inhibition in human neurons.…”

Section: Resultsmentioning

confidence: 76%

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

et al. 2014

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Assessment of the network of toxicity pathways by Omics technologies and bioinformatic data processing paves the road toward a new toxicology for the twenty-first century. Especially, the upstream network of responses, taking place in toxicant-treated cells before a point of no return is reached, is still little explored. We studied the effects of the model neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) by a combined metabolomics (mass spectrometry) and transcriptomics (microarrays and deep sequencing) approach to provide unbiased data on earliest cellular adaptations to stress. Neural precursor cells (LUHMES) were differentiated to homogeneous cultures of fully postmitotic human dopaminergic neurons, and then exposed to the mitochondrial respiratory chain inhibitor MPP+ (5 μM). At 18–24 h after treatment, intracellular ATP and mitochondrial integrity were still close to control levels, but pronounced transcriptome and metabolome changes were seen. Data on altered glucose flux, depletion of phosphocreatine and oxidative stress (e.g., methionine sulfoxide formation) confirmed the validity of the approach. New findings were related to nuclear paraspeckle depletion, as well as an early activation of branches of the transsulfuration pathway to increase glutathione. Bioinformatic analysis of our data identified the transcription factor ATF-4 as an upstream regulator of early responses. Findings on this signaling pathway and on adaptive increases of glutathione production were confirmed biochemically. Metabolic and transcriptional profiling contributed complementary information on multiple primary and secondary changes that contribute to the cellular response to MPP+. Thus, combined ‘Omics' analysis is a new unbiased approach to unravel earliest metabolic changes, whose balance decides on the final cell fate.

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Section: Resultsmentioning

confidence: 76%

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

et al. 2014

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“…In addition, we detected several new RNA splicing or RNA binding proteins in the AGO2 IPs. For example, SFPQ/NONO heteromer, which is an essential premRNA splicing factor required for spliceosome formation and splicing catalytic step II [25], was abundant in both tumor and its NAT tissues. NUDT21, which is a cleavage factor required for 3′ RNA cleavage and polyadenylation processing [26], was detected in tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

et al. 2015

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“…*, P Ͻ 0.05; **, P Ͻ 0.01; ***, P Ͻ 0.001. 45), thus controlling isoform and splice variant expression. Our study provides further support for the role of p54 nrb / NONO in regulating RNA processing.…”

Section: As Discussed Above P54mentioning

confidence: 99%

p54^nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation

Lee

Sewer

2015

Molecular and Cellular Biology

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Glucocorticoid production in the adrenal cortex is activated in response to an increase in cyclic AMP (cAMP) signaling. The nuclear protein p54 nrb /NONO belongs to the Drosophila behavior/human splicing (DBHS) family and has been implicated in several nuclear processes, including transcription, splicing, and RNA export. We previously identified p54 nrb /NONO as a component of a protein complex that regulates the transcription of CYP17A1, a gene required for glucocorticoid production. Based on the multiple mechanisms by which p54 nrb /NONO has been shown to control gene expression and the ability of the protein to be recruited to the CYP17A1 promoter, we sought to further define the molecular mechanism by which p54 nrb /NONO confers optimal cortisol production. We show here that silencing p54 nrb /NONO expression in H295R human adrenocortical cells decreases the ability of the cells to increase intracellular cAMP production and subsequent cortisol biosynthesis in response to adrenocorticotropin hormone (ACTH) stimulation. Interestingly, the expression of multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A, PDE4D, and PDE11A, was induced in p54 nrb /NONO knockdown cells. Investigation of the mechanism by which silencing of p54 nrb /NONO led to increased expression of select PDE isoforms revealed that p54 nrb /NONO regulates the splicing of a subset of PDE isoforms. Importantly, we also identify a role for p54 nrb /NONO in regulating the stability of PDE transcripts by facilitating the interaction between the exoribonuclease XRN2 and select PDE transcripts. In summary, we report that p54 nrb /NONO modulates cAMP-dependent signaling, and ultimately cAMP-stimulated glucocorticoid biosynthesis by regulating the splicing and degradation of PDE transcripts. T he non-POU domain-containing octamer-binding protein p54nrb /NONO is a member of the Drosophila behavior/human splicing (DBHS) family of RNA-binding proteins and is comprised of two tandem RNA recognition motif (RRM) domains followed by a charged protein-protein interaction module (1-3). DBHS proteins have been described as multifunctional nuclear proteins, with p54 nrb /NONO being implicated in numerous nuclear processes, including transcription regulation, mRNA splicing, nuclear retention, and subnuclear body formation (4-7). In addition to binding to DNA elements such as intracisternal A particles (8), p54 nrb /NONO is also known to promote the binding of other transcription factors to their response elements (9). The polypyrimidine tract-binding protein-associated splicing factor (PSF)/p54 nrb /NONO heterodimer regulates the transcriptional activity of several nuclear receptors (NRs), including the thyroid hormone receptor (10) and the androgen receptor (11). This heterodimeric complex also promotes nuclear retention of hyperedited RNAs by binding to the inner nuclear matrix structural protein matrin 3 (12, 13) and stimulates topoisomerase I activity (14). A heterodimer of p54 nrb /NONO and paraspeckle protein 1 has been shown to be...

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hnRNP M interacts with PSF and p54nrb and co-localizes within defined nuclear structures

Cited by 49 publications

References 38 publications

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

p54^nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation

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hnRNP M interacts with PSF and p54nrb and co-localizes within defined nuclear structures

Cited by 49 publications

References 38 publications

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP+

PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

p54nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation

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p54^nrb/NONO Regulates Cyclic AMP-Dependent Glucocorticoid Production by Modulating Phosphodiesterase mRNA Splicing and Degradation