期刊
GENOME BIOLOGY
卷 22, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13059-021-02369-0
关键词
Pseudogene; PacBio; Long-read; lncRNA; CRISPR
资金
- Australian Department of Health Medical Frontiers Future Fund (MRFF) [MRF1175457]
- Australian National Health and Medical Research Council (NHMRC) [GNT1173711, GNT1161832]
- CSL Centenary Fellowship
- University of Queensland Early Career Researcher Grant
- Mater Foundation (Equity Trustees/AE Hingeley Trust)
Pseudogenes, once considered as functionless relics of evolution, are now recognized as a complex and dynamic component of the human transcriptional landscape. This study identified hundreds of novel transcribed pseudogenes expressed in tissue-specific patterns, some of which have intact open reading frames and encode proteins. Deleting the nucleus-enriched pseudogene PDCL3P4 using CRISPR-Cas9 led to perturbations in hundreds of genes, highlighting the potential biological impact of noncoding pseudogenes.
Pseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. Using deep full-length PacBio cDNA sequencing of normal human tissues and cancer cell lines, we identify here hundreds of novel transcribed pseudogenes expressed in tissue-specific patterns. Some pseudogene transcripts have intact open reading frames and are translated in cultured cells, representing unannotated protein-coding genes. To assess the biological impact of noncoding pseudogenes, we CRISPR-Cas9 delete the nucleus-enriched pseudogene PDCL3P4 and observe hundreds of perturbed genes. This study highlights pseudogenes as a complex and dynamic component of the human transcriptional landscape.
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