Pumilio and nanos RNA-binding proteins counterbalance the transcriptional consequences of RB1 inactivation

Miles, Wayne; Dyson, Nicholas J.

doi:10.4161/23723548.2014.968074

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Loss of the DRM subunit lethal (3) malignant brain tumor [l(3)mbt] leads to tumorous growth in Drosophila imaginal disks and ectopic expression of germline genes, including nanos ( Janic et al, 2010 ). Similarly, loss of the retinoblastoma transcription factor (Rb) leads to activation of nanos transcription in mammalian tissue culture cells and in Drosophila wings, which in turn is thought to repress the translation of Rb targets ( Miles and Dyson, 2014 ; Miles et al, 2014 ). A complex regulatory feedback loop has also been reported between the LSD1 demethylase and the Nanos partner Pumilio in Drosophila and human bladder carcinoma cells ( Miles et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

Lee

Seydoux

2017

eLife

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Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

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Section: Discussionmentioning

confidence: 99%

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

Lee

Seydoux

2017

eLife

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“…4 There are also areas within the 3 0 -UTR that can bind to repressor proteins to suppress the expression of mRNA. 5 Many 3 0 -UTRs include the ARE element that is rich in AUs, which can affect the start of translation. 6 In addition to the sequence, the physical properties of the 3 0 -UTR, including its length and secondary structure, also affect translation control.…”

Section: Introductionmentioning

confidence: 99%

Study on 3′-UTR length polymorphism in peripheral blood mononuclear cells of uremia patient

et al. 2015

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Objective: The objective of this study was to measure the 3 0 -untranslated region (3 0 -UTR) polymorphism lengths in peripheral blood mononuclear cells (PBMCs) from uremia patients. Method: We sequenced the alternative polyadenylation sites in the 3 0 -UTR of PBMCs from 10 uremic patients and 10 healthy people to detect different gene expression levels between uremia patients and healthy controls. Quantitative reverse transcription polymerase chain reaction was used as validation. Result: Compared with the healthy control group, 691 genes in uremic patients had significantly different 3 0 -UTR lengths. Of these genes, 475 genes showed shortened 3 0 -UTRs, and the 3 0 -UTRs of 216 genes were lengthened. The verification results matched the original sequencing results. Conclusion: There were significant differences in 3 0 -UTR lengths between uremic patients and healthy controls, and analysis of the differential genes may contribute to the understanding of uremia pathogenesis.

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Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

Lee

Seydoux

2017

Preprint

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The Nanos RNA-binding protein has been implicated in the specification of primordial germ cells (PGCs) in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of PGCs away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity.

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Pumilio and nanos RNA-binding proteins counterbalance the transcriptional consequences of RB1 inactivation

Cited by 3 publications

References 9 publications

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

Study on 3′-UTR length polymorphism in peripheral blood mononuclear cells of uremia patient

Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

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