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Dissolution of RNA condensates by the embryonic stem cell protein L1TD1

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227856 | GEO | 2023/04/26

REPOSITORIES: GEO

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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 [CLIP-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 | GSE227855 | GEO

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

2023-04-26 | GSE227854 | GEO

Dissolution of RNA condensates by the embryonic stem cell protein L1TD1

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

| PRJNA947184 | ENA

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]

| PRJNA947189 | ENA

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]

| PRJNA947191 | ENA

EZH2-RNA interactions in embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-10-19 | E-GEOD-49435 | biostudies-arrayexpress

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

2018-02-02 | GSE80454 | GEO

Bacterial Stress Bodies – Ancestral Condensates Regulating RNA Turnover and Protein Translation

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

2024-04-01 | GSE241322 | GEO

Derivation of monkey parthenogenetic haploid embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-06-26 | E-GEOD-43980 | biostudies-arrayexpress

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