Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome
| Autor: | Seth W. Cheetham, Geoffrey J. Faulkner, Yohaann M. A. Jafrani, Robin-Lee Troskie, Adam D. Ewing, Tim R. Mercer |
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| Rok vydání: | 2021 |
| Předmět: |
DNA
Complementary QH301-705.5 Pseudogene Short Report Computational biology Haploidy QH426-470 Biology ENCODE Cell Line Transcriptome lncRNA Genetics Humans CRISPR Gene silencing Biology (General) ORFS Promoter Regions Genetic Gene PacBio Sequence Analysis DNA Human genetics Open reading frame RNA splicing Long-read Cdna sequencing Gene Deletion Pseudogenes |
| Zdroj: | Genome Biology, Vol 22, Iss 1, Pp 1-15 (2021) Genome Biology |
| DOI: | 10.1101/2021.03.29.437610 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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