The role of vault RNA-derived small RNA in gene expression regulation
Vault RNA are small non-coding polymerase III transcribed RNA, which are a crucial com- ponent of a large ribonucleoprotein complex called Vault. Despite only 5% of vault RNA being associated with the Vault complex, little is known about their Vault-independent cellular roles. Here I show that vtRNA...
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Format: | Thesis |
Language: | English |
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2022
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author | Terenova, J |
author2 | Gullerova, M |
author_facet | Gullerova, M Terenova, J |
author_sort | Terenova, J |
collection | OXFORD |
description | Vault RNA are small non-coding polymerase III transcribed RNA, which are a crucial com- ponent of a large ribonucleoprotein complex called Vault. Despite only 5% of vault RNA being associated with the Vault complex, little is known about their Vault-independent cellular roles. Here I show that vtRNA are processed by Dicer into functional small vault RNA (svtRNA) fragments that associate with Argonaute 2. Nascent RNA sequencing revealed the highest number of predicted svtRNA1-2 target genes among up-regulated genes, in AGO2 and Dicer Knock Down cells, compared to other svtRNA. svtRNA1-2 target sites were detected predominantly in the intronic regions. Genomic deletion of vtRNA1-2 results in the severe inhibition of proliferation and up-regulation of genes sig- nificantly associated with cell membrane physiology, including ERBB4 and cell adhesion. Finally, I show that svtRNA1-2 hybridises to target genes in a dual-region complemen- tarity and loop protrusion is required for intron targeting. These results show a novel small vault RNA1-2 with a role in gene expression regulation, possessing unique molecular features for targeting genes in introns leading to nascent RNA silencing. |
first_indexed | 2024-03-07T07:27:10Z |
format | Thesis |
id | oxford-uuid:4ce0d55d-56da-4935-94c0-c57155d8b514 |
institution | University of Oxford |
language | English |
last_indexed | 2024-12-09T03:48:10Z |
publishDate | 2022 |
record_format | dspace |
spelling | oxford-uuid:4ce0d55d-56da-4935-94c0-c57155d8b5142024-12-08T11:06:12ZThe role of vault RNA-derived small RNA in gene expression regulationThesishttp://purl.org/coar/resource_type/c_db06uuid:4ce0d55d-56da-4935-94c0-c57155d8b514Non-coding RNAMolecular biologyBioinformaticsEnglishHyrax Deposit2022Terenova, JGullerova, MBaena Lopez, LAChelysheva, IVault RNA are small non-coding polymerase III transcribed RNA, which are a crucial com- ponent of a large ribonucleoprotein complex called Vault. Despite only 5% of vault RNA being associated with the Vault complex, little is known about their Vault-independent cellular roles. Here I show that vtRNA are processed by Dicer into functional small vault RNA (svtRNA) fragments that associate with Argonaute 2. Nascent RNA sequencing revealed the highest number of predicted svtRNA1-2 target genes among up-regulated genes, in AGO2 and Dicer Knock Down cells, compared to other svtRNA. svtRNA1-2 target sites were detected predominantly in the intronic regions. Genomic deletion of vtRNA1-2 results in the severe inhibition of proliferation and up-regulation of genes sig- nificantly associated with cell membrane physiology, including ERBB4 and cell adhesion. Finally, I show that svtRNA1-2 hybridises to target genes in a dual-region complemen- tarity and loop protrusion is required for intron targeting. These results show a novel small vault RNA1-2 with a role in gene expression regulation, possessing unique molecular features for targeting genes in introns leading to nascent RNA silencing. |
spellingShingle | Non-coding RNA Molecular biology Bioinformatics Terenova, J The role of vault RNA-derived small RNA in gene expression regulation |
title | The role of vault RNA-derived small RNA in gene expression regulation |
title_full | The role of vault RNA-derived small RNA in gene expression regulation |
title_fullStr | The role of vault RNA-derived small RNA in gene expression regulation |
title_full_unstemmed | The role of vault RNA-derived small RNA in gene expression regulation |
title_short | The role of vault RNA-derived small RNA in gene expression regulation |
title_sort | role of vault rna derived small rna in gene expression regulation |
topic | Non-coding RNA Molecular biology Bioinformatics |
work_keys_str_mv | AT terenovaj theroleofvaultrnaderivedsmallrnaingeneexpressionregulation AT terenovaj roleofvaultrnaderivedsmallrnaingeneexpressionregulation |