Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/138401
DC Field | Value | |
---|---|---|
dc.title | DEAH BOX HELICASE 9 (DHX9) AS A BIDIRECTIONAL REGULATOR IN ADENOSINE-TO-INOSINE (A-TO-I) EDITING | |
dc.contributor.author | HONG HUIQI | |
dc.date.accessioned | 2018-01-16T18:00:30Z | |
dc.date.available | 2018-01-16T18:00:30Z | |
dc.date.issued | 2017-08-14 | |
dc.identifier.citation | HONG HUIQI (2017-08-14). DEAH BOX HELICASE 9 (DHX9) AS A BIDIRECTIONAL REGULATOR IN ADENOSINE-TO-INOSINE (A-TO-I) EDITING. ScholarBank@NUS Repository. | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/138401 | |
dc.description.abstract | Adenosine-to-Inosine (A-to-I) editing entails the enzymatic deamination of adenosines to inosines by Adenosine DeAminases acting on RNA (ADARs). Substrate structures play a central role in substrate selectivity and specificity of ADARs. RNA helicases, a family of ATP-driven enzymes remodelling RNA structures and ribonucleoprotein complexes may therefore have a regulatory role in A-to-I editing. In our study, we elucidated the regulatory roles of DEAH-box helicase 9 (DHX9) in A-to-I editing. ADARs and DHX9 form a complex in the nucleus, the primary site of A-to-I editing. To investigate the functional role of DHX9 in editing, we examined the global editome upon DHX9 knockdown using RNA sequencing. Intriguingly, we uncovered that DHX9 functions as a bidirectional regulator and the direction of change is largely dependent on the ADAR specificity of the sites. DHX9 knockdown represses editing of ADAR1-specific substrates and augments editing of ADAR2-specific substrates. The failure to rescue the knockdown phenotype with DHX9 helicase mutant (DHX9K417R) indicates that the helicase activity is essential for A-to-I editing regulation. In sum, DHX9 constitutes a bidirectional mode of regulation in A-to-I editing. Functionally, DHX9 is an essential gene as DHX9 suppression has deleterious effects on foci formation, anchorage-independent growth and in vivo xenograft tumour formation. | |
dc.language.iso | en | |
dc.subject | Helicase, DEAH box helicase 9 DHX9, RNA editing, adenosine-to-inosine editing, regulator, post transcriptional modification | |
dc.type | Thesis | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.supervisor | Chen Leilei | |
dc.contributor.supervisor | Daniel G. Tenen | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY (CSI) | |
Appears in Collections: | Ph.D Theses (Open) |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
HongHuiQi_PhD thesis_FINAL-signed.pdf | 4.36 MB | Adobe PDF | OPEN | None | View/Download |
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.