Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer

Delaunay, Sylvain; Rapino, Francesca; Tharun, Lars; Zhou, Zhaoli; Heukamp, Lukas C.; Termathe, Martin; Shostak, Kateryna; Klevernic, Iva; Florin, Alexandra; Desmecht, Hadrien; Desmet, Christophe; Nguyen, Laurent; Leidel, Sebastian A.; Willis, Anne E.; Büttner, Reinhard; Chariot, Alain; Close, Pierre

doi:10.1084/jem.20160397

Cited by 143 publications

(122 citation statements)

References 77 publications

(119 reference statements)

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“…This indicated that MYCBP may be one of the targets of LEF-1. LEF-1 has previously been reported to be expressed excessively and to function as an oncogene in numerous types of cancer (36). Furthermore, the TCF/LEF axis serves a crucial role in the Wnt/β-catenin signaling pathway, and the Wnt signaling pathway has been shown to be involved in a number of cellular functions, including cell proliferation, survival, and differentiation (37,38).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

et al. 2018

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Abstract. Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the β-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

et al. 2018

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“…For example, the enzymes responsible for mcm 5 s 2 modification, ELP3 and CTU1/2, have been found to be up-regulated in breast cancer and to sustain metastasis (Delaunay et al 2016). Similarly, the methyltransferase NSUN2 has been found to be overexpressed in breast cancer and its expression levels have been shown to correlate with cancer development and progression .…”

Section: Wwwrnajournalorg 1759mentioning

confidence: 99%

The RNA modification landscape in human disease

Jonkhout

Tran

Smith

et al. 2017

RNA

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RNA modifications have been historically considered as fine-tuning chemo-structural features of infrastructural RNAs, such as rRNAs, tRNAs, and snoRNAs. This view has changed dramatically in recent years, to a large extent as a result of systematic efforts to map and quantify various RNA modifications in a transcriptome-wide manner, revealing that RNA modifications are reversible, dynamically regulated, far more widespread than originally thought, and involved in major biological processes, including cell differentiation, sex determination, and stress responses. Here we summarize the state of knowledge and provide a catalog of RNA modifications and their links to neurological disorders, cancers, and other diseases. With the advent of direct RNA-sequencing technologies, we expect that this catalog will help prioritize those RNA modifications for transcriptome-wide maps.

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“…In regard to tRNA modifications, their functions include: stability and flexibility of the tRNA structure (Motorin and Helm 2010), translational fidelity via codon-anticodon interaction (Saint-Léger and Ribas de Pouplana 2015), reading frame maintenance (Waas et al 2007;Delaunay et al 2016;Klassen et al 2016a), tRNA discrimination , nonsense suppression (Benko et al 2000), tRNA stability (Alexandrov et al 2006;Kotelawala et al 2008;Dewe et al 2012), proteome integrity (Nedialkova and Leidel 2015), sensitivity to aminoglycoside antibiotics acting at the decoding site of ribosomes (Kalhor and Clarke 2003), response to stress (Kamenski et al 2007;Chan et al 2012;Gu et al 2014), and recognition of tRNA as either self or nonself by TLR7 receptor (Kaiser et al 2014;Rimbach et al 2015). For general reviews, see Helm (2011), Hopper (2013) and Phizicky and Hopper (2015).…”

Section: The State Of the Trna Population In The Cellmentioning

confidence: 99%

“…Their alterations result in severe consequences during translation, such as misreading, frame shifts, translation shifted to another distant site, as well as diverse pleiotropic cellular effects, including pathological states (Wei and Tomizawa 2011;Delaunay et al 2016). The three cases are clear examples of the links between tRNA modification and the cellular metabolic state.…”

Section: The State Of the Trna Population In The Cellmentioning

confidence: 99%

Protein folding and tRNA biology

2017

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Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.

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Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer

Abstract: Delaunay et al. reveal the role of U34 tRNA-modifying enzymes in the regulation of specific mRNA translation to support cell invasion and metastasis.

Cited by 143 publications

References 77 publications

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

The RNA modification landscape in human disease

Protein folding and tRNA biology

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