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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Main Author: Terenova, J
Other Authors: Gullerova, M
Format: Thesis
Language:English
Published: 2022
Subjects:
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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.
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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
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