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A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies

ABSTRACT: A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies

PROVIDER: PRJNA559859 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9952650.fastq.gz	Fastqsanger.gz
	SRR9952660.fastq.gz	Fastqsanger.gz
	SRR9952670.fastq.gz	Fastqsanger.gz
	SRR9952651.fastq.gz	Fastqsanger.gz
	SRR9952661.fastq.gz	Fastqsanger.gz

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A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies

Project description:In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and in vivo ribosome profiling, we observe limb patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos and uncover selective translational changes of transcripts controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are explained by the identification that p53 functions as a master regulator of protein synthesis, at least in part, through transcriptional activation of 4E-BP1. 4E-BP1, a key translational regulator, in turn, facilitates selective changes in the translatome downstream of p53, and thereby explains how RP haploinsufficiency may elicit specificity to gene expression. These results provide an integrative model to understand how in vivo tissue-specific phenotypes emerge in ribosomopathies.

2021-05-09 | GSE135722 | GEO

A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.

Project description:In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and in vivo ribosome profiling, we observe limb-patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos, and we uncover selective translational changes of transcripts that controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are explained by the finding that p53 functions as a master regulator of protein synthesis, at least in part, through transcriptional activation of 4E-BP1. 4E-BP1, a key translational regulator, in turn, facilitates selective changes in the translatome downstream of p53, and this thereby explains how RP haploinsufficiency may elicit specificity to gene expression. These results provide an integrative model to help understand how in vivo tissue-specific phenotypes emerge in ribosomopathies.

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Elk1 Directs a Critical Component of Growth Signaling by the Androgen Receptor in Prostate Cancer

Project description:Elk1 directs selective gene induction that is a substantial and critical component of growth signaling by AR in PC cells.

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Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding

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Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor

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Elk1 Directs a Critical Component of Growth Signaling by the Androgen Receptor in Prostate Cancer

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TIA proteins drives global and specific translational repression of genes linked to the cell-cycle progression and DNA replication/repair

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