An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation
Abstract Background Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements requir...
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12977-021-00580-2 |
| _version_ | 1818837881632849920 |
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| author | Koichi Kitao So Nakagawa Takayuki Miyazawa |
| author_facet | Koichi Kitao So Nakagawa Takayuki Miyazawa |
| author_sort | Koichi Kitao |
| collection | DOAJ |
| description | Abstract Background Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs. Results Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence. Conclusions These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses. |
| first_indexed | 2024-12-19T03:29:33Z |
| format | Article |
| id | doaj.art-aa9f67d7d2b34872b681de4e7a345f48 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-19T03:29:33Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-aa9f67d7d2b34872b681de4e7a345f482022-12-21T20:37:33ZengBMCRetrovirology1742-46902021-11-0118111510.1186/s12977-021-00580-2An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulationKoichi Kitao0So Nakagawa1Takayuki Miyazawa2Laboratory of Virus-Host Coevolution, Institute for Frontier Life and Medical Sciences, Kyoto UniversityDepartment of Molecular Life Science, Tokai University School of MedicineLaboratory of Virus-Host Coevolution, Institute for Frontier Life and Medical Sciences, Kyoto UniversityAbstract Background Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs. Results Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence. Conclusions These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.https://doi.org/10.1186/s12977-021-00580-2Endogenous retrovirusesRNA regulatory elementSyncytinMammalian genomes |
| spellingShingle | Koichi Kitao So Nakagawa Takayuki Miyazawa An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation Retrovirology Endogenous retroviruses RNA regulatory element Syncytin Mammalian genomes |
| title | An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation |
| title_full | An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation |
| title_fullStr | An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation |
| title_full_unstemmed | An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation |
| title_short | An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation |
| title_sort | ancient retroviral rna element hidden in mammalian genomes and its involvement in co opted retroviral gene regulation |
| topic | Endogenous retroviruses RNA regulatory element Syncytin Mammalian genomes |
| url | https://doi.org/10.1186/s12977-021-00580-2 |
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