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Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome

Isaac A Babarinde1,2, Gang Ma1,2, Yuhao Li1,2

  • 1Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.

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|August 14, 2021
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Summary
This summary is machine-generated.

Transposable elements (TEs) are integrated into many human transcripts, impacting their function and regulation. This study reveals widespread TE sequence incorporation in human pluripotent stem cells (hPSCs), affecting RNA stability and localization.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Transposable elements (TEs) constitute a significant portion of mammalian genomes.
  • While often inactive, TEs can influence cellular functions.
  • The extent of TE sequence contribution to mature RNA transcripts is not fully understood.

Purpose of the Study:

  • To investigate the prevalence and functional impact of transposable element (TE) sequences within RNA transcripts in human pluripotent stem cells (hPSCs).
  • To characterize the patterns of TE incorporation and their effects on RNA structure, localization, and stability.
  • To identify specific TE families and their roles in hPSCs and during differentiation.

Main Methods:

  • Utilized long and short read RNA sequencing (LR and SR) to analyze TE sequences in transcripts.
  • Employed single-cell RNA sequencing (scRNA-seq) to examine TE expression in different cell populations.
  • Integrated analysis of RNA Binding Proteins (RBPs) and subcellular distribution to understand functional consequences.

Main Results:

  • TE-derived sequences were found in 26% of coding and 65% of noncoding transcripts in hPSCs.
  • TE families exhibit distinct incorporation patterns, influencing transcript structure and function.
  • TE presence correlates with altered subcellular distribution, stability, and RBP association.
  • hPSCs specifically incorporate endogenous retroviruses (ERVs) and LINE:L1 into mRNAs, producing TE-derived peptides.
  • Differentiating cells lose ERV transcripts but retain SINE and LINE elements.

Conclusions:

  • TE sequence incorporation into RNA is a widespread phenomenon in hPSCs with significant functional implications.
  • Specific TE families, like ERVs and LINE:L1, play unique roles in hPSC biology and differentiation.
  • This study highlights a previously underestimated impact of TEs on the transcriptome and cellular function.