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Related Experiment Video

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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation

Published on: June 17, 2015

L1 mobile element expression causes multiple types of toxicity.

Nicholas A Wallace¹, Victoria P Belancio, Prescott L Deininger

¹Tulane Cancer Center, SL66, and Department of Epidemiology, Tulane University Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA.

|June 17, 2008

Summary

LINE-1 retrotransposons significantly reduce cellular vitality. Their expression, particularly ORF2, triggers apoptosis and a senescence-like state, impacting cell health.

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Area of Science:

Genomics
Molecular Biology
Cellular Biology

Background:

LINE-1 (L1) retrotransposons are abundant in the human genome (≥17%) and their expression can harm cells.
L1 expression is linked to genomic instability (mutagenesis, deletions, rearrangements, DNA breaks) and apoptosis.
Previous studies correlated L1 expression with cancer progression, necessitating further investigation into its cellular effects.

Purpose of the Study:

To investigate the impact of LINE-1 retrotransposon expression on cellular viability.
To identify the specific L1 components responsible for decreased cellular vitality.

Main Methods:

Cellular models were used to express LINE-1 retrotransposons.
Analysis focused on the role of the second open reading frame (ORF2) and its domains (endonuclease, reverse transcriptase).
Cellular vitality, apoptosis, and senescence were assessed.

Main Results:

LINE-1 expression markedly decreased overall cellular vitality.
This decrease was primarily dependent on the second open reading frame (ORF2).
Both ORF2's endonuclease and reverse transcriptase domains independently contributed to reduced cellular vitality.
L1 expression induced both apoptosis and a senescence-like state.

Conclusions:

LINE-1 retrotransposon expression significantly impairs cellular viability through multiple mechanisms.
ORF2 is a key determinant of L1's deleterious effects on cells.
L1 impacts cellular health by inducing both programmed cell death (apoptosis) and cellular aging (senescence).