2013
DOI: 10.1038/nature12119
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A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway

Abstract: The pluripotency factor Lin28 blocks the expression of let-7 microRNAs (miRNAs) in undifferentiated cells during development and functions as an oncogene in a subset of cancers1. Lin28 binds to let-7 precursor RNAs and recruits 3′ terminal uridylyl transferases (TUTases) to selectively inhibit let-7 biogenesis2–4. Uridylated pre-let-7 is refractory to processing by Dicer and is rapidly degraded by an unknown ribonuclease5. Here we identify Dis3l2 as the 3′-5′ exonuclease responsible for the decay of uridylated… Show more

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Cited by 297 publications
(347 citation statements)
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“…The post-transcriptional levels of LET-7 mi RNAs are regulated by LIN28, which is overexpressed in multiple types of tumours including Wilms, and the expression of which correlates with tumour aggressiveness 221 . Moreover, LIN28 overexpression induces Wilms tumours in mice 222 . LIN-28 targets LET-7 pre-mi RNAs for degradation by polyuridylating them at their 3ʹ end, which targets them for degradation by the DIS3-like exonuclease 2 (DIS3L2) 223,224 (FIG.…”
Section: Mechanisms Of Mirna Dysregulationmentioning
confidence: 99%
“…The post-transcriptional levels of LET-7 mi RNAs are regulated by LIN28, which is overexpressed in multiple types of tumours including Wilms, and the expression of which correlates with tumour aggressiveness 221 . Moreover, LIN28 overexpression induces Wilms tumours in mice 222 . LIN-28 targets LET-7 pre-mi RNAs for degradation by polyuridylating them at their 3ʹ end, which targets them for degradation by the DIS3-like exonuclease 2 (DIS3L2) 223,224 (FIG.…”
Section: Mechanisms Of Mirna Dysregulationmentioning
confidence: 99%
“…26 Total RNA samples were collected for real-time PCR assay to detect the relative gene expression. To detect the poly-uridylated pre-let7g, small RNAs (<200 bp) were first isolated with mirVana miRNA Isolation Kit (Life Technologies), then same amount of isolated small RNA samples were used for the reverse transcription with oligodA12 and subsequent real-time PCR analysis.…”
Section: In Vitro Uridylation Assaymentioning
confidence: 99%
“…To detect the poly-uridylated pre-let7g, small RNAs (<200 bp) were first isolated with mirVana miRNA Isolation Kit (Life Technologies), then same amount of isolated small RNA samples were used for the reverse transcription with oligodA12 and subsequent real-time PCR analysis. 26 PPi light assay The PPi light assay was performed with the PPiLight TM Inorganic Pyrophosphate Assay kit (Lonza). Briefly, reaction system containing 50 ng rZcchc11 protein, 50 mM UTP, 0.75 mM let7i synthetic guide RNA, 4 units of RNasin (Promega), and PPi substrates was incubated at 37 C for 30 mins.…”
Section: In Vitro Uridylation Assaymentioning
confidence: 99%
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“…In humans and the yeast S. pombe, this is often achieved by addition of a polyuridine (polyU) tract to the 3' end of the transcript which provides an ideal landing pad for DIS3L2 to initiate/reinitiate 3'-5' decay [14][15][16]. As well as mRNAs, miRNAs such as pre-let-7 have been shown to be poly-uridylated and then degraded by DIS3L2 in human cells and mouse embryonic stem cells [17,18].…”
Section: Introductionmentioning
confidence: 99%