WEE Keng Boon

PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells

Published date : 09 Jul 2018

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1.

type
Journal Paper
journal
Cancer Cell, Vol. 34, Issue 1, Pg 85-102, 9 July 2018, doi: 10.1016/j.ccell.2018.06.007,
Impact Factor
22.844

SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

Published date : 19 Jun 2018

The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte.

type
Journal Paper
journal
Cell Discovery 4, Article no: 33 (2018), doi: 10.1038/s41421-018-0032-3
Impact Factor
4.462

RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

Published date : 09 Jun 2016

Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification.

type
Journal Paper
journal
Cell Reports 15, 1–11, June 21, 2016
Impact Factor
7.87

Discovery of Influenza A Virus Sequence Pairs and Their Combinations for Simultaneous Heterosubtypic Targeting that Hedge against Antiviral Resistance

Published date : 15 Jan 2016

The multiple circulating human influenza A virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. The capacity to drug most RNAs motivates the investigation on viral RNA targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans–H1N1, 2009 pandemic H1N1, H3N2, H5N1 and H7N9, were used to identify 1,183 conserved RNA target sequences (≥15-mer) in the internal segments.

type
Journal Paper
journal
PLOS Computational Biology, 15 Jan 2016, doi: 10.1371/journal.pcbi.1004663
Impact Factor
4.829

MYC regulates the the core pre-mRNA splicing machinery as an an essential step in lymphomagenesis

Published date : 11 May 2015

Deregulated expression of the MYC transcription factor occurs in most human cancers and correlates with high proliferation, reprogrammed cellular metabolism and poor prognosis1. Overexpressed MYC binds to virtually all active promoters within a cell, although with different binding affinities2, 3, 4, and modulates the expression of distinct subsets of genes1, 2, 4, 5. However, the critical effectors of MYC in tumorigenesis remain largely unknown.

type
Journal Paper
journal
Nature 2015, doi:10.1038/nature14351
Impact Factor
42.351