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Dissolution of RNA condensates by the embryonic stem cell protein L1TD1

ABSTRACT: Dissolution of RNA condensates by the embryonic stem cell protein L1TD1

PROVIDER: PRJNA947184 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23932253.fastq.gz	Fastqsanger.gz
	SRR23932254.fastq.gz	Fastqsanger.gz
	SRR23932255.fastq.gz	Fastqsanger.gz
	SRR23932256.fastq.gz	Fastqsanger.gz
	SRR23932257.fastq.gz	Fastqsanger.gz

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Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [RNA-seq]

Project description:L1TD1 is a cytoplasmic RNA-binding protein that is specifically expressed in pluripotent stem cells and, unlike its mouse paralogue, is essential for the maintenance of stemness in human cells. Although L1TD1 is the only known domesticated gene from a LINE-1 (L1) retroelement, the functional legacy from its ancestral protein, ORF1p of L1, and the novelty are so far unknown. Here, we determined RNAs associated with L1TD1 and found that, like ORF1p, L1TD1 binds L1 RNAs, localizes to high-density ribonucleoprotein (RNP) condensates, and increases L1 retrotransposition. Unexpectedly, L1TD1 enhanced the translation of a subset of mRNAs enriched in the condensates. In HeLa cells, ectopically expressed L1TD1 facilitated the dissolution of stress granules and granules formed by pathological mutations of TDP-43 and FUS. The glutamate-rich domain and the ORF1-homology domain facilitated dispersal of the RNPs and induced autophagy, respectively. These results provide insights into how L1TD1 regulates gene expression in pluripotent stem cells. We propose that the ability of L1TD1 to dissolve stress granules may provide novel opportunities for treatments of neurodegenerative diseases caused by disturbed stress granule dynamics.

2023-04-26 | GSE227854 | GEO

Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [CLIP-seq]

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Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [RNA-seq]

Project description:Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [RNA-seq]

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Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [CLIP-seq]

Project description:Dissolution of RNA condensates by the embryonic stem cell protein L1TD1 [CLIP-seq]

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Dissolution of ribonucleoprotein condensates by the embryonic stem cell protein L1TD1.

Project description:L1TD1 is a cytoplasmic RNA-binding protein specifically expressed in pluripotent stem cells and, unlike its mouse ortholog, is essential for the maintenance of stemness in human cells. Although L1TD1 is the only known protein-coding gene domesticated from a LINE-1 (L1) retroelement, the functional legacy of its ancestral protein, ORF1p of L1, and how it is manifested in L1TD1 are still unknown. Here, we determined RNAs associated with L1TD1 and found that, like ORF1p, L1TD1 binds L1 RNAs and localizes to high-density ribonucleoprotein (RNP) condensates. Unexpectedly, L1TD1 enhanced the translation of a subset of mRNAs enriched in the condensates. L1TD1 depletion promoted the formation of stress granules in embryonic stem cells. In HeLa cells, ectopically expressed L1TD1 facilitated the dissolution of stress granules and granules formed by pathological mutations of TDP-43 and FUS. The glutamate-rich domain and the ORF1-homology domain of L1TD1 facilitated dispersal of the RNPs and induced autophagy, respectively. These results provide insights into how L1TD1 regulates gene expression in pluripotent stem cells. We propose that the ability of L1TD1 to dissolve stress granules may provide novel opportunities for treatment of neurodegenerative diseases caused by disturbed stress granule dynamics.

| S-EPMC11014241 | biostudies-literature

Dissolution of RNA condensates by the embryonic stem cell protein L1TD1

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-26 | GSE227856 | GEO

Prevalent aberrant condensates of onco-fusion transcription factors and their dissolution as potential cancer therapy

Project description:Prevalent aberrant condensates of onco-fusion transcription factors and their dissolution as potential cancer therapy

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Metabolomics Workbench ST000003 - GNPS - Metabolomic analysis of mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells

Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis

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Hijacking of transcriptional condensates by endogenous retroviruses

Project description:Heterochromatin plays essential roles in repressing retrotransposons, e.g. endogenous retroviruses (ERVs) during mammalian development, but the contribution of retrotransposition to lethality observed in embryonic cells deficient for heterochromatin-mediated ERV repression is poorly understood. Here we report that selective degradation of the TRIM28 heterochromatin adapter protein leads to reduced association of transcriptional condensates with loci encoding super-enhancer -driven pluripotency genes in embryonic stem cells, a collapse of the pluripotency transcriptional circuit, and a pre-lethal restriction of pluripotent lineages in mouse embryos. De-repressed ERVs recruit transcriptional condensates in the absence of TRIM28, and ERV RNA facilitates condensation of RNA Polymerase II in vitro. We propose that retrotransposons contribute to the genomic distribution of nuclear condensates, and that RNA species may facilitate “hijacking” of transcriptional condensates in various developmental and disease contexts.

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Prevalent aberrant condensates of onco-fusion transcription factors and their dissolution as potential cancer therapy

Project description:Cancer-associated chromosomal rearrangements can result in the expression of numerous pathogenic fusion proteins. The mechanisms via which the fusion proteins contribute to oncogenesis are largely unknown and effective therapies for fusion-associated cancers are lacking. Here, we comprehensively scrutinized fusion proteins found in various cancers. We found that many fusion proteins are composed of phase separation-prone domains (PS) and DNA-binding domains (DBD), and these fusions have strong correlation with aberrant gene expression patterns. Furthermore, we established a high-throughput screening method, named DropScan, to screen drugs capable of modulating aberrant condensates. One of the drugs identified via DropScan, LY2835219, effectively dissolved the condensates in reporter cells lines expressing Ewing sarcoma fusions and partially rescued the abnormal expression of target genes. Our results indicate that aberrant phase separation is likely a common mechanism for these PS-DBD fusion-related cancers, and suggest that modulating aberrant phase separation is a potential route to treat these diseases.

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