Identification of cell-type-specific, transcriptionally active transposable elements using long-read RNA-sequencing...

Area of Science:

• Genomics
• Transcriptomics
• Molecular Biology

Background:

• Biological functions of transposable element (TE)-derived transcripts are known, but locus-specific expression in human cells is understudied.
• Limited research exists on the role of TE-derived transcripts in various human cell types.

Purpose of the Study:

• To create the first transcriptomic annotation for TE-derived transcripts.
• To enable the detection of locus-specific TE-derived transcripts in diverse human cell types.
• To provide a comprehensive reference for analyzing TE transcription.

Main Methods:

• Processed 2596 human long-read RNA sequencing (LR RNA-seq) datasets from 21 organs and 71 cell lines.
• Developed a pipeline to assemble transcripts containing TE sequences.
• Applied the TE annotation to Genotype-Tissue Expression (GTEx) single-cell RNA sequencing (scRNA-seq) data.

Main Results:

• Constructed a comprehensive TE-derived transcript annotation, outperforming existing methods like RepeatMasker and GENCODE.
• Identified novel TE-derived transcripts, isoforms, and alternative transcription end sites for long noncoding genes.
• Discovered cell-type-specific TE-derived transcripts in human tissues using scRNA-seq data.

Conclusions:

• Generated a comprehensive TE-derived transcript annotation from large-scale LR RNA-seq data.
• The annotation serves as a valuable resource for analyzing active TE transcripts and their isoforms.
• Discovered cell-type-specific TE transcripts that may elucidate cellular identity maintenance and disease pathology.