Evidence for widespread existence of functional novel and non-canonical human transcripts
Abstract Background Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of functi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-023-01753-5 |
| _version_ | 1797451453454876672 |
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| author | Dongyang Xu Lu Tang Junjun Zhou Fang Wang Huifen Cao Yu Huang Philipp Kapranov |
| author_facet | Dongyang Xu Lu Tang Junjun Zhou Fang Wang Huifen Cao Yu Huang Philipp Kapranov |
| author_sort | Dongyang Xu |
| collection | DOAJ |
| description | Abstract Background Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches. Results In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs. Conclusions Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions. |
| first_indexed | 2024-03-09T14:54:52Z |
| format | Article |
| id | doaj.art-1682f5f597db41ec819fa044823ad045 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-03-09T14:54:52Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-1682f5f597db41ec819fa044823ad0452023-11-26T14:14:35ZengBMCBMC Biology1741-70072023-11-0121113110.1186/s12915-023-01753-5Evidence for widespread existence of functional novel and non-canonical human transcriptsDongyang Xu0Lu Tang1Junjun Zhou2Fang Wang3Huifen Cao4Yu Huang5Philipp Kapranov6Institute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityInstitute of Genomics, School of Medicine, Huaqiao UniversityAbstract Background Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches. Results In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs. Conclusions Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions.https://doi.org/10.1186/s12915-023-01753-5Insertional mutagenesisFunctional genomicsRNA dark matterNon-canonical transcriptNovel exonAlternative splicing |
| spellingShingle | Dongyang Xu Lu Tang Junjun Zhou Fang Wang Huifen Cao Yu Huang Philipp Kapranov Evidence for widespread existence of functional novel and non-canonical human transcripts BMC Biology Insertional mutagenesis Functional genomics RNA dark matter Non-canonical transcript Novel exon Alternative splicing |
| title | Evidence for widespread existence of functional novel and non-canonical human transcripts |
| title_full | Evidence for widespread existence of functional novel and non-canonical human transcripts |
| title_fullStr | Evidence for widespread existence of functional novel and non-canonical human transcripts |
| title_full_unstemmed | Evidence for widespread existence of functional novel and non-canonical human transcripts |
| title_short | Evidence for widespread existence of functional novel and non-canonical human transcripts |
| title_sort | evidence for widespread existence of functional novel and non canonical human transcripts |
| topic | Insertional mutagenesis Functional genomics RNA dark matter Non-canonical transcript Novel exon Alternative splicing |
| url | https://doi.org/10.1186/s12915-023-01753-5 |
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