Translation initiation in cancer at a glance

Smith, Rachael C. L.; Kanellos, Georgios; Vlahov, Nikola; Alexandrou, C.; Willis, Anne E.; Knight, John R. P.; Sansom, Owen J.

doi:10.1242/jcs.248476

Cited by 32 publications

(34 citation statements)

References 134 publications

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“…m6A is the most abundant RNA internal modification in eukaryotes [ 86 ]. This modification mostly occurs in the shared motif “RRm6ACH” (R = G or A; H = A, C, or U) [ 87 ], affecting multiple stages of RNA localization, splicing, translation, and degradation [ 69 ]. m6A is catalyzed by a methyltransferase complex composed of METTL3, METL14, Wilms tumor-associated protein, RBM15/15B, Virma, and ZC3H13 [ 88 , 89 ] and by cellulite and obesity-related proteins (FTO) and ALKB homolog 3/5 (ALKBH3/5) demethylated [ 90 – 92 ].…”

Section: Circrna Translation Mechanismmentioning

confidence: 99%

“…This mechanism is called the the capdependent translation pathway [66,67], and the main mechanism of eukaryotic translation initiation, but is not the only mechanism. Under certain circumstances, such as stress, a cap-independent translation mechanism is present in the body [68][69][70]. The cap-independent translation pathway is the underlying mechanism of CircRNA translation.…”

Section: Circrna Translation Mechanismmentioning

confidence: 99%

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Circular RNAs’ cap-independent translation protein and its roles in carcinomas

Man

Xiang

et al. 2021

Mol Cancer

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Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.

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Section: Circrna Translation Mechanismmentioning

confidence: 99%

Section: Circrna Translation Mechanismmentioning

confidence: 99%

Circular RNAs’ cap-independent translation protein and its roles in carcinomas

Man

Xiang

et al. 2021

Mol Cancer

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“…Translation can be regulated at many steps and has been recently reviewed [ 103 , 104 , 105 ]; here, we focus on the initiation step. eIF4E-dependent translation initiation is considered as the “reference” pathway in that regard (see recent reviews [ 14 , 104 , 106 ]). In this pathway, once mRNAs are in the cytoplasm, the multi-protein translation initiation complex eIF4F assembles on the m 7 G cap of the RNA [ 107 ].…”

Section: Rna Maturation Nuclear Export and Translation Focusing On The Roles Of Cap-chaperonesmentioning

confidence: 99%

The Cap-Binding Complex CBC and the Eukaryotic Translation Factor eIF4E: Co-Conspirators in Cap-Dependent RNA Maturation and Translation

Mars

Ghram

Culjkovic-Kraljacic

et al. 2021

Cancers

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The translation of RNA into protein is a dynamic process which is heavily regulated during normal cell physiology and can be dysregulated in human malignancies. Its dysregulation can impact selected groups of RNAs, modifying protein levels independently of transcription. Integral to their suitability for translation, RNAs undergo a series of maturation steps including the addition of the m7G cap on the 5′ end of RNAs, splicing, as well as cleavage and polyadenylation (CPA). Importantly, each of these steps can be coopted to modify the transcript signal. Factors that bind the m7G cap escort these RNAs through different steps of maturation and thus govern the physical nature of the final transcript product presented to the translation machinery. Here, we describe these steps and how the major m7G cap-binding factors in mammalian cells, the cap binding complex (CBC) and the eukaryotic translation initiation factor eIF4E, are positioned to chaperone transcripts through RNA maturation, nuclear export, and translation in a transcript-specific manner. To conceptualize a framework for the flow and integration of this genetic information, we discuss RNA maturation models and how these integrate with translation. Finally, we discuss how these processes can be coopted by cancer cells and means to target these in malignancy.

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“…In non-transformed cells, phosphorylation of eIF2α on Ser51 inhibits the formation of the initiation complex and attenuates general translation. Remarkably, in cancer cells, p-eIF2α promotes oncogenic translation; phosphorylation of eIF2α in cancer cells “hijacks” the translation machinery and results in enhanced activation of tumor-promoting translation via the use of non-conventional internal ribosome entry site (IRES)-containing oncogenic mRNAs and involves unique translation machinery including proteins such as eIF5B, eIF2D, and MCT-1 that together activate tumor promoting pathways [ 128 , 129 , 130 ].…”

Section: The Tumor-promoting Activity Of Rnf4mentioning

confidence: 99%

From the Evasion of Degradation to Ubiquitin-Dependent Protein Stabilization

Ahmad

Oknin-Vaisman

Bitman-Lotan

et al. 2021

Cells

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A hallmark of cancer is dysregulated protein turnover (proteostasis), which involves pathologic ubiquitin-dependent degradation of tumor suppressor proteins, as well as increased oncoprotein stabilization. The latter is due, in part, to mutation within sequences, termed degrons, which are required for oncoprotein recognition by the substrate-recognition enzyme, E3 ubiquitin ligase. Stabilization may also result from the inactivation of the enzymatic machinery that mediates the degradation of oncoproteins. Importantly, inactivation in cancer of E3 enzymes that regulates the physiological degradation of oncoproteins, results in tumor cells that accumulate multiple active oncoproteins with prolonged half-lives, leading to the development of “degradation-resistant” cancer cells. In addition, specific sequences may enable ubiquitinated proteins to evade degradation at the 26S proteasome. While the ubiquitin-proteasome pathway was originally discovered as central for protein degradation, in cancer cells a ubiquitin-dependent protein stabilization pathway actively translates transient mitogenic signals into long-lasting protein stabilization and enhances the activity of key oncoproteins. A central enzyme in this pathway is the ubiquitin ligase RNF4. An intimate link connects protein stabilization with tumorigenesis in experimental models as well as in the clinic, suggesting that pharmacological inhibition of protein stabilization has potential for personalized medicine in cancer. In this review, we highlight old observations and recent advances in our knowledge regarding protein stabilization.

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Translation initiation in cancer at a glance

Cited by 32 publications

References 134 publications

Circular RNAs’ cap-independent translation protein and its roles in carcinomas

Circular RNAs’ cap-independent translation protein and its roles in carcinomas

The Cap-Binding Complex CBC and the Eukaryotic Translation Factor eIF4E: Co-Conspirators in Cap-Dependent RNA Maturation and Translation

From the Evasion of Degradation to Ubiquitin-Dependent Protein Stabilization

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