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Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome

ABSTRACT: Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome

PROVIDER: PRJNA673144 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12933206_subreads.fastq.gz	Fastqsanger.gz
	SRR12933207_subreads.fastq.gz	Fastqsanger.gz
	SRR14338438_1.fastq.gz	Fastqsanger.gz
	SRR14338438_2.fastq.gz	Fastqsanger.gz
	SRR14338439_1.fastq.gz	Fastqsanger.gz

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Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome

Project description:Pseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. When transcribed, pseudogenes may encode proteins or enact RNA-intrinsic regulatory mechanisms. However, the extent, characteristics and functional relevance of the human pseudogene transcriptome are unclear. Short-read sequencing platforms have limited power to resolve and accurately quantify pseudogene transcripts owing to the high sequence similarity of pseudogenes and their parent genes. Using deep full-length PacBio cDNA sequencing of normal human tissues and cancer cell lines, we identify here hundreds of novel transcribed pseudogenes. Pseudogene transcripts are expressed in tissue-specific patterns, exhibit complex splicing patterns and contribute to the coding sequences of known genes. We survey pseudogene transcripts encoding intact open reading frames (ORFs), representing potential unannotated protein-coding genes, and demonstrate their efficient translation in cultured cells. To assess the impact of noncoding pseudogenes on the cellular transcriptome, we delete the nucleus-enriched pseudogene PDCL3P4 transcript from HAP1 cells and observe hundreds of perturbed genes. This study highlights pseudogenes as a complex and dynamic component of the transcriptional landscape underpinning human biology and disease.

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