송호석 (고려대학교 구로병원)

한빛사논문

조회576

송호석Hoseok Song

고려대학교 구로병원

Nucleic Acids Res., Jan 02 2024, gkad1244 | https://doi.org/10.1093/nar/gkad1244 Dissolution of ribonucleoprotein condensates by the embryonic stem cell protein L1TD1

Sang Woo Jin^1,†, Youngmo Seong^1,†, Dayoung Yoon^1,†, Young-Soo Kwon^2,*and Hoseok Song^1,*

¹Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea

²Department of Integrative Bioscience & Biotechnology, Sejong University, Seoul 05006, Republic of Korea

^*To whom correspondence should be addressed. : Hoseok Song

Correspondence may also be addressed to Young-Soo Kwon.

^†The first three authors should be regarded as Joint First Authors.

Abstract

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.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-03)
연구진국내 연구진
분야 생명과학 > 세포생물학

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