A5033204736- RNA Research and Splicing
- RNA regulation and disease
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Virus-based gene therapy research
- Cancer Genomics and Diagnostics
National University Cancer Institute, Singapore
2016-2024
National University of Singapore
2016-2024
GlobalFoundries (Singapore)
2020
Abstract RNA editing and splicing are the two major processes that dynamically regulate human transcriptome diversity. Despite growing evidence of crosstalk between enzymes (mainly ADAR1) machineries, detailed mechanistic explanations their biological importance in diseases, such as cancer still lacking. Herein, we identify approximately a hundred high-confidence events altered by ADAR1 and/or ADAR2, or ADAR2 protein can cassette exons both directions. We unravel binding tendency ADARs to...
Abstract Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) known to bind double-stranded for adenosine inosine (A-to-I) editing. Here we characterize ADARs as potent regulators circular transcriptome identifying over a thousand circRNAs regulated bidirectional manner through and beyond their editing function. We find that...
Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) expression target genes undergoing extensive 3′UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3′UTR, demonstrate that could be repressed beyond their...
Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on (ADARs). Dysregulated A-to-I has been implicated in various diseases, including cancers. However, precise factors governing and their physiopathological implications remain as a long-standing question. Herein, we unravel that DEAH box helicase 9 (DHX9), at least partially dependent its activity, functions bidirectional regulator cancer cells. Intriguingly,...
RNA editing introduces nucleotide changes in sequences. Recent studies have reported that aberrant adenosine-to-inosine is implicated cancers. Until now, very few functionally important protein-recoding targets been discovered. Here, we investigated the role of a recently discovered target COPA (coatomer subunit α) hepatocellular carcinoma (HCC).Clinical implication was studied cohort 125 HCC patients. CRISPR/Cas9-mediated knockout site complementary sequence (ECS) used to delete edited...
DAP3 represses adenosine-to-inosine (A-to-I) RNA editing in cancer cells and promotes progression.
The dynamic regulation of alternative splicing requires coordinated participation multiple RNA binding proteins (RBPs). Aberrant caused by dysregulation regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as RBP cancer. Mechanistically, DAP3 coordinates networks, not only via mediating the formation ribonucleoprotein complexes to induce substrate-specific changes, but also modulating factors cause indirect effect on...
Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available inhibitors have so far been developed to inhibit cancer-associated events. Here, we decipher the secondary structure of antizyme inhibitor 1 (AZIN1), one best-studied A-to-I targets cancer, by locating its site complementary sequence (ECS) at 3′ end exon 12. Chemically modified antisense oligonucleotides (ASOs) that target region AZIN1 caused a substantial 11 skipping, whereas...
Abstract Adenosine-to-inosine (A-to-I) editing, catalysed by Adenosine DeAminases acting on double-stranded RNA (dsRNA) (ADAR), occurs predominantly in the 3’ untranslated regions (3’UTRs). Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) expression of target genes undergoing extensive 3’UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor as exemplary gene, demonstrate that its could be repressed beyond their editing dsRNA binding functions....