An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication
Here we show that the adenovirus major late promoter produces a 31-nucleotide transcriptional start site small RNA (MLP-TSS-sRNA) that retains the 7-methylguanosine (m7G)-cap and is incorporated onto Ago2-containing RNA-induced silencing complexes (RISC) in human adenovirus-37 infected cells. RNA po...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Cold Spring Harbor Laboratory
2017
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| _version_ | 1797068665942704128 |
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| author | Kamel, W Akusjärvi, G |
| author_facet | Kamel, W Akusjärvi, G |
| author_sort | Kamel, W |
| collection | OXFORD |
| description | Here we show that the adenovirus major late promoter produces a 31-nucleotide transcriptional start site small RNA (MLP-TSS-sRNA) that retains the 7-methylguanosine (m7G)-cap and is incorporated onto Ago2-containing RNA-induced silencing complexes (RISC) in human adenovirus-37 infected cells. RNA polymerase II CLIP (UV-cross linking immunoprecipitation) experiments suggest that the MLP-TSS-sRNA is produced by promoter proximal stalling/termination of RNA polymerase II transcription at the site of the small RNA 3′ end. The MLP-TSS-sRNA is highly stable in cells and functionally active, down-regulating complementary targets in a sequence and dose-dependent manner. The MLP-TSS-sRNA is transcribed from the opposite strand to the adenoviral DNA polymerase and preterminal protein mRNAs, two essential viral replication proteins. We show that the MLP-TSS-sRNA act in trans to reduce DNA polymerase and preterminal protein mRNA expression. As a consequence of this, the MLP-TSS-sRNA has an inhibitory effect on the efficiency of viral DNA replication. Collectively, our results suggest that this novel sRNA may serve a regulatory function controlling viral genome replication during a lytic and/or persistent adenovirus infection in its natural host. |
| first_indexed | 2024-03-06T22:13:27Z |
| format | Journal article |
| id | oxford-uuid:5299b8c4-f4ef-4171-a665-b2de62d14340 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:13:27Z |
| publishDate | 2017 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | dspace |
| spelling | oxford-uuid:5299b8c4-f4ef-4171-a665-b2de62d143402022-03-26T16:26:28ZAn Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replicationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5299b8c4-f4ef-4171-a665-b2de62d14340EnglishSymplectic ElementsCold Spring Harbor Laboratory2017Kamel, WAkusjärvi, GHere we show that the adenovirus major late promoter produces a 31-nucleotide transcriptional start site small RNA (MLP-TSS-sRNA) that retains the 7-methylguanosine (m7G)-cap and is incorporated onto Ago2-containing RNA-induced silencing complexes (RISC) in human adenovirus-37 infected cells. RNA polymerase II CLIP (UV-cross linking immunoprecipitation) experiments suggest that the MLP-TSS-sRNA is produced by promoter proximal stalling/termination of RNA polymerase II transcription at the site of the small RNA 3′ end. The MLP-TSS-sRNA is highly stable in cells and functionally active, down-regulating complementary targets in a sequence and dose-dependent manner. The MLP-TSS-sRNA is transcribed from the opposite strand to the adenoviral DNA polymerase and preterminal protein mRNAs, two essential viral replication proteins. We show that the MLP-TSS-sRNA act in trans to reduce DNA polymerase and preterminal protein mRNA expression. As a consequence of this, the MLP-TSS-sRNA has an inhibitory effect on the efficiency of viral DNA replication. Collectively, our results suggest that this novel sRNA may serve a regulatory function controlling viral genome replication during a lytic and/or persistent adenovirus infection in its natural host. |
| spellingShingle | Kamel, W Akusjärvi, G An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title | An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title_full | An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title_fullStr | An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title_full_unstemmed | An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title_short | An Ago2-associated capped transcriptional start site small RNA suppresses adenovirus DNA replication |
| title_sort | ago2 associated capped transcriptional start site small rna suppresses adenovirus dna replication |
| work_keys_str_mv | AT kamelw anago2associatedcappedtranscriptionalstartsitesmallrnasuppressesadenovirusdnareplication AT akusjarvig anago2associatedcappedtranscriptionalstartsitesmallrnasuppressesadenovirusdnareplication AT kamelw ago2associatedcappedtranscriptionalstartsitesmallrnasuppressesadenovirusdnareplication AT akusjarvig ago2associatedcappedtranscriptionalstartsitesmallrnasuppressesadenovirusdnareplication |