Sun et al. 2021 (PRJNA753487)

Title	An oncomicropeptide Regulates translation in leukemia
Organism
Number of Samples	4
Release Date	2021/08/10 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Sun L,Wang W,Han C,Huang W,Sun Y,Fang K,Zeng Z,Yang Q,Pan Q,Chen T,Luo X,Chen Y
Journal	Molecular cell
Publication Date	2021 Nov 4
Abstract	Initiation is the rate-limiting step in translation, and its dysregulation is vital for carcinogenesis, including hematopoietic malignancy. Thus, discovery of novel translation initiation regulators may provide promising therapeutic targets. Here, combining Ribo-seq, mass spectrometry, and RNA-seq datasets, we discovered an oncomicropeptide, APPLE (a peptide located in ER), encoded by a non-coding RNA transcript in acute myeloid leukemia (AML). APPLE is overexpressed in various subtypes of AML and confers a poor prognosis. The micropeptide is enriched in ribosomes and regulates the initiation step to enhance translation and to maintain high rates of oncoprotein synthesis. Mechanically, APPLE promotes PABPC1-eIF4G interaction and facilitates mRNA circularization and eIF4F initiation complex assembly to support a specific pro-cancer translation program. Targeting APPLE exhibited broad anti-cancer effects in vitro and in vivo. This study not only reports a previously unknown function of micropeptides but also provides new opportunities for targeting the translation machinery in cancer cells. Copyright © 2021 Elsevier Inc. All rights reserved.
PMC
PMID	34555354
DOI

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