Transposable element–gene chimera cartography, origination and role in enhancing transcriptome plasticity
Youngseo Cheon, Erik Glen Alvstad, Denis Torre, Daniel Tu Quach, Jennifer Nguyen, Kwangbeom Hyun, Mingqi Zhou, Tianxiong Yu, Liang Liu, Yoseop Yoon, Fairlie Reese, Lauren Faraone, Yingcong Li, Frederick J. Arnold, Yesai S. Fstkchyan, Uttiya Basu, Evgeny Kvon, Enza Maria Valente
TL;DR
The paper explores how transposable elements contribute to gene expression and cell function by forming gene hybrids and influencing RNA regulation.
Contribution
The study introduces a new method to map transposable element-derived gene isoforms and identifies RNA-based quality control mechanisms.
Findings
TE-derived isoforms vary between mouse and human and are linked to regulatory networks during development and disease.
An RNA degradation and splicing-dependent quality control mechanism prevents TE-chimera expression independently of DNA methylation.
TE-derived elements enhance transcriptome plasticity by influencing gene regulation and cell differentiation.
Abstract
Transposable elements (TEs) in the human genome are the heritage of ancient parasitic infections. While most of human DNA comprises TEs and TE-derived elements, their repetitive nature poses technical challenges; thus, little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigate when, where and how TEs become part of a gene. We characterize how TE-derived isoforms change across mouse–human variation and how they are linked to gene regulatory networks controlling cell states during differentiation, organogenesis and health (aging and pathological states). Mechanistically, we identify an RNA degradation-dependent and splicing-dependent quality control mechanism that operates independently of conventional mechanisms of TE suppression, such as DNA methylation and heterochromatinization, and…
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Taxonomy
TopicsChromosomal and Genetic Variations · RNA modifications and cancer · Chromatin Remodeling and Cancer