Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation.
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ABSTRACT:
SUBMITTER: Toda T
PROVIDER: S-EPMC10948021 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
Publications
Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation.
Toda Tomohisa T Bedrosian Tracy A TA Schafer Simon T ST Cuoco Michael S MS Linker Sara B SB Ghassemzadeh Saeed S Mitchell Lisa L Whiteley Jack T JT Novaresi Nicole N McDonald Aidan H AH Gallina Iryna S IS Yoon Hyojung H Hester Mark E ME Pena Monique M Lim Christina C Suljic Emelia E AlFatah Mansour Abed A Boulard Matthieu M Parylak Sarah L SL Gage Fred H FH
Cell reports 20240213 2
Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, L1s are paradoxically expressed at high levels in differentiating neural progenitor cells. Using in vitro and in vivo techniques to modulate L1 expression, we report that L1s play a critical role in both human a ...[more]
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Project description:BackgroundLong Interspersed Nuclear Element-1 (LINE-1) is an autonomous retrotransposon that generates new genomic insertions through the retrotransposition of a RNA intermediate. Expression of LINE-1 is tightly repressed in most somatic tissues to prevent DNA damage and ensure genomic integrity. However, the reactivation of LINE-1 has been documented in cancer and the role of LINE-1 protein expression and retrotransposition has become of interest in the development, progression, and adaptation of many epithelial neoplasms, including prostate cancer.ResultsHere, we examined endogenous LINE-1 protein expression and localization in a panel of prostate cancer cells and observed a diverse range of LINE-1 expression patterns between cell lines. Subcellular localization of LINE-1 proteins, ORF1p and ORF2p, revealed distinct expression patterns. ORF1p, a nucleic acid chaperone that binds LINE-1 mRNA, was predominantly expressed in the cytoplasm, with minor localization in the nucleus. ORF2p, containing endonuclease and reverse transcriptase domains, exhibited punctate foci in the nucleus and also displayed co-localization with PCNA and γH2AX. Using a retrotransposition reporter assay, we found variations in LINE-1 retrotransposition between cell lines.ConclusionsOverall, our findings reveal new insight into the expression and retrotransposition of LINE-1 in prostate cancer. The prostate cancer cells we investigated provide a unique model for investigating endogenous LINE-1 activity and provide a functional model for studying LINE-1 mechanisms in prostate cancer.
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