Awards & Achievements

CSI PhD Student Selected to Give a Presentation at 5th Heidelberg Forum for Young Life Scientists!

Congratulations to our CSI PhD student Hong Huiqi from Dr Polly Chen’s lab!

Huiqi’s abstract titled ‘DEAH Box Helicase 9 (DHX9) as a Bidirectional Regulator of Adenosine-to-Inosine (A-to-I) Editing’ was selected for presentation at the 5th Heidelberg Forum for Young Life Scientists. Along with the selection of her abstract, Huiqi was also awarded a travel grant and will be heading to Heidelberg, Germany in June 2017.

The Heidelberg Forum for Young Life Scientists (HFYLS) is a bi-annual scientific symposium organized by PhD students working in the field of life sciences in Heidelberg and Mannheim, Germany. The forum seeks to bring together young scientists from all over the world, from a broad range of life-science-related disciplines, for a two-day conference. In doing so, they will also foster interdisciplinary exchange and provide new insights into a broad range of current research topics.

The 2017 forum, titled “A Tale of Cells & Organisms”, will be held from 8-9 June at the German Cancer Research Center (DKFZ). There are four sections at the forum, namely Translational Cancer Research, Aging, Microbiota and Signaling, and Huiqi’s presentation will take place at the Translational Cancer Research section.

DEAH box Helicase 9 (DHX9) as a bidirectional regulator of Adenosine-to-Inosine (A-to-I) editing

HuiQi HONG1, Tim Hon Man CHAN1, Huisi KWOK1, Omer AN1, Vanessa Hui En NG1, Henry YANG1, Ying LI1, Daniel G. TENEN1,2 and Leilei CHEN1,3

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore
2 Harvard Stem Cell Institute, Harvard Medical School, Boston, MA
3 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract:

Adenosine-to-Inosine (A-to-I) editing, a post-transcriptional modification catalysed by Adenosine Deaminases Acting on RNAs (ADARs), contributes to transcriptome and proteome diversity as the general cellular machineries decode inosines as guanosines. A-to-I editing plays a cardinal role in physiological and pathophysiological settings. Specifically, dysregulated A-to-I editing is linked to various cancers including hepatocellular carcinoma, gastric and esophageal cancers. To date, it remains elusive how ADARs select their substrates. The lack of sequence similarity in editing substrates strongly suggests that substrate structure, instead of the sequence, plays a more pivotal role in determining substrate specificity of ADARs. We identified DEAH box helicase 9 (DHX9) in our global screening for ADAR-interacting factors. DHX9 co-localises with ADARs in the nucleus, the primary site of A-to-I editing. As a RNA helicase, DHX9 has the ability to restructure transcripts and therefore may affect A-to-I editing through structural remodelling. In our study, RNA-seq of DHX9 knockdown cells uncovered both hypo- and hyper-editing events, thereby suggesting that DHX9 functions as a bidirectional regulator in A-to-I editing. The failure of DHX9 helicase mutant (DHX9K417R) to rescue the knockdown phenotype indicates that the helicase activity is essential. Lastly, we established the functional importance of DHX9 helicase activity, as helicase mutant is incapable of rescuing cell viability, foci formation, anchorage-independent cell proliferation and xenograft growth of DHX9 knockdown cells.