Posttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1).
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractSelected long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis. Although the cellular functions of these transcripts can be diverse, many lncRNAs regulate gene expression. In contrast, factors that control the expression of lncRNAs remain largely unknown. Here we investigated the impact of RNA binding proteins on the expression of the liver cancer-associated lncRNA HULC (highly up-regulated in liver cancer). First, we validated the strong up-regulation of HULC in human hepatocellular carcinoma. To elucidate posttranscriptional regulatory mechanisms governing HULC expression, we applied an RNA affinity purification approach to identify specific protein interaction partners and potential regulators. This method identified the family of IGF2BPs (IGF2 mRNA-binding proteins) as specific binding partners of HULC. Depletion of IGF2BP1, also known as IMP1, but not of IGF2BP2 or IGF2BP3, led to an increased HULC half-life and higher steady-state expression levels, indicating a posttranscriptional regulatory mechanism. Importantly, HULC represents the first IGF2BP substrate that is destabilized. To elucidate the mechanism by which IGF2BP1 destabilizes HULC, the CNOT1 protein was identified as a novel interaction partner of IGF2BP1. CNOT1 is the scaffold of the human CCR4-NOT deadenylase complex, a major component of the cytoplasmic RNA decay machinery. Indeed, depletion of CNOT1 increased HULC half-life and expression. Thus, IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA HULC. Conclusion: Our findings provide important insights into the regulation of lncRNA expression and identify a novel function for IGF2BP1 in RNA metabolism. (Hepatology 2013).
CitationPosttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1). 2013: Hepatology
AffiliationAG Genomanalytic, Hemholtz Centre for Infection research, D38124 Braunschweig, Germany
JournalHepatology (Baltimore, Md.)
The following license files are associated with this item:
- Long noncoding RNA HULC modulates the phosphorylation of YB-1 through serving as a scaffold of extracellular signal-regulated kinase and YB-1 to enhance hepatocarcinogenesis.
- Authors: Li D, Liu X, Zhou J, Hu J, Zhang D, Liu J, Qiao Y, Zhan Q
- Issue date: 2017 May
- Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC.
- Authors: Gandhy SU, Imanirad P, Jin UH, Nair V, Hedrick E, Cheng Y, Corton JC, Kim K, Safe S
- Issue date: 2015 Sep 22
- Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion.
- Authors: Cao SQ, Zheng H, Sun BC, Wang ZL, Liu T, Guo DH, Shen ZY
- Issue date: 2019 Sep 21
- Long noncoding RNA HULC promotes hepatocellular carcinoma progression.
- Authors: Zhang H, Liao Z, Liu F, Su C, Zhu H, Li Y, Tao R, Liang H, Zhang B, Zhang X
- Issue date: 2019 Oct 23
- Long Noncoding RNA Highly Up-regulated in Liver Cancer Predicts Unfavorable Outcome and Regulates Metastasis by MMPs in Triple-negative Breast Cancer.
- Authors: Shi F, Xiao F, Ding P, Qin H, Huang R
- Issue date: 2016 Aug