BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//NUS CSI - ECPv6.11.0.1//NONSGML v1.0//EN
CALSCALE:GREGORIAN
METHOD:PUBLISH
X-ORIGINAL-URL:https://csi.nus.edu.sg
X-WR-CALDESC:Events for NUS CSI
REFRESH-INTERVAL;VALUE=DURATION:PT1H
X-Robots-Tag:noindex
X-PUBLISHED-TTL:PT1H
BEGIN:VTIMEZONE
TZID:UTC
BEGIN:STANDARD
TZOFFSETFROM:+0000
TZOFFSETTO:+0000
TZNAME:UTC
DTSTART:20190101T000000
END:STANDARD
END:VTIMEZONE
BEGIN:VEVENT
DTSTART;TZID=UTC:20190226T030000
DTEND;TZID=UTC:20190226T040000
DTSTAMP:20260418T022321
CREATED:20230120T001609Z
LAST-MODIFIED:20230120T001609Z
UID:47848-1551150000-1551153600@csi.nus.edu.sg
SUMMARY:RNA Biology Centre Meeting - 26 Feb
DESCRIPTION:Venue: Level 12 Conference Room\nTime: 11am \nScientific work presentation: \nSpeaker: Xin Yi LOH (Prof H. Phillip Koeffler’s group) \nTitle: ZFP36L1 suppresses hypoxia and cell cycle signaling \nAbstract: \nZFP36L1 is a tandem zinc-finger RNA binding protein (RBP) that recognizes conserved Adenylate-Uridylate-rich elements (AU-rich elements\, AREs) located in 3’untranslated regions (UTRs) mediating mRNAs decay process. Here\, we hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involving in mRNA half-life regulation of cancer-related transcripts. To identify the direct downstream targets of ZFP36L1\, a systematic screening using RNA pull-down and whole transcriptome sequencing of bladder cancer cells ± ZFP36L1 was performed. Analysis of in silico data revealed that ZFP36L1 is significantly mutated\, epigenetically silenced and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced in vitro and in vivo cell proliferation; whereas silencing of ZFP36L1 enhanced tumor cells growth. We identified a network of 1\,410 targets\, which were bound by wildtype\, but not zinc finger mutant ZFP36L1. These targets included a number of key oncogenic transcripts\, such as HIF-1?\, CCND1 and E2F1. ZFP36L1 specifically bound to 3’UTRs of these targets for mRNA degradation\, thus suppressing their mRNA and protein expressions. Dual luciferase reporter assays and RNA Electro-Mobility Shift Assays (RNA-EMSA) showed that wildtype\, but not zinc finger mutant ZFP36L1\, bound to HIF-1? 3’UTR and mediated HIF-1? mRNA degradation. This eventually leads to reduced expressions of HIF-1? and its downstream targets in metabolism and angiogenesis. Collectively\, our findings shed light on the pathophysiology of bladder tumorigenesis and revealed an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
URL:https://csi.nus.edu.sg/event/rna-biology-centre-meeting-26-feb/
END:VEVENT
END:VCALENDAR