Cap-Independent Translation: What’s in a Name?

Shatsky, Ivan N.; Terenin, Ilya M.; Smirnova, Victoria V.; Andreev, Dmitry E.

doi:10.1016/j.tibs.2018.04.011

Cited by 99 publications

(92 citation statements)

References 94 publications

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“…In particular, the methyl group linked to the N7 amine of guanosine in the m 7 G cap ensures RNA recognition by eukaryotic translation initiation factor 4E for cap-dependent translation initiation (3). Cap-independent translation can occur via the recognition of other features in mRNAs, such as internal ribosome entry sites or m 6 A modification (4).…”

mentioning

confidence: 99%

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Yuan

Zhao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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As the most common RNA cap in eukaryotes, the 7-methylguanosine (m7G) cap impacts nearly all processes that a messenger RNA undergoes, such as splicing, polyadenylation, nuclear export, translation, and degradation. The metabolite and redox agent, nicotinamide adenine diphosphate (NAD+), can be used as an initiating nucleotide in RNA synthesis to result in NAD+-capped RNAs. Such RNAs have been identified in bacteria, yeast, and human cells, but it is not known whether they exist in plant transcriptomes. The functions of the NAD+ cap in RNA metabolism or translation are still poorly understood. Here, through NAD captureSeq, we show that NAD+-capped RNAs are widespread in Arabidopsis thaliana. NAD+-capped RNAs are predominantly messenger RNAs encoded by the nuclear and mitochondrial genomes, but not the chloroplast genome. NAD+-capped transcripts from the nuclear genome appear to be spliced and polyadenylated. Furthermore, although NAD+-capped transcripts constitute a small proportion of the total transcript pool from any gene, they are enriched in the polysomal fraction and associate with translating ribosomes. Our findings implicate the existence of as yet unknown mechanisms whereby the RNA NAD+ cap interfaces with RNA metabolic processes as well as translation initiation. More importantly, our findings suggest that cellular metabolic and/or redox states may influence, or be regulated by, mRNA NAD+ capping.

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confidence: 99%

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Yuan

Zhao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…However, no common structural motifs were identified among the cellular IRES elements and, compared to viral IRES, cellular IRES elements appear to be much more diverse and less stable in terms of Gibbs free energy of folding (40). In contrast to these reports, it has recently been proposed that other cellular mRNAs may recruit ribosomal PICs in an capindependent manner to the 5' end using a CITE that recruits eIFs, and that the ribosomal PIC then scans from the 5' end rather than using an IRES to initiate translation internally (19). Given the fact that some 5' UTRs may possess either IRESs and/or CITEs, we were prompted to test the hypothesis that the free 5' end of our selected 5' UTRs is required for translation.…”

Section: Discussionmentioning

confidence: 97%

“…The subset of mRNAs that is translated cap-independently under stress conditions as described above are predicted to contain highly stable structures in their 5' untranslated regions (UTRs) that may act as internal ribosome entry sites (IRES) or cap-independent translation enhancers (CITEs) (5,16). IRES-like mechanisms involve direct recruitment of the ribosome to structured IRESs that are close to the AUG start codon (5,17), while CITE-like mechanisms involve direct recruitment of eIFs to structured CITEs near the 5' end of the mRNA, where the eIFs are then thought to initiate cap-independent translation via 48S PIC scanning to the AUG start codon (18,19). Although chemical and enzymatic probing of cellular mRNAs thought to contain IRESs/CITEs have revealed stem loops, pseudoknots, and other structures (20,21), no common sequence or structural motifs have been identified to allow prediction of cellular IRESs/CITEs from mRNA sequence data.…”

Section: Introductionmentioning

confidence: 99%

5’ UTR recruitment of eIF4GI or DAP5 drives cap-independent translation for a subset of human mRNAs

Sa¹,

Bhardwaj²,

Gonzalez³

et al. 2018

Preprint

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Running title: eIF4GI or DAP5 drives cap-independent translation initiationKeywords: 5' CITE | IRES | eIF4GI | DAP5 | fluorescence anisotropy AbstractDuring unfavorable human cellular conditions (e.g., tumor hypoxia, viral infection, etc.), canonical, cap-dependent mRNA translation is suppressed. Nonetheless, a subset of physiologically important mRNAs (e.g., HIF-1α, FGF-9, and p53) is still translated by an unknown, capindependent mechanism. Additionally, expression levels of eIF4G and its homolog, death associated protein 5 (DAP5), are elevated. Using fluorescence anisotropy binding studies, luciferase reporter-based in vitro translation assays, and mutational analyses, here we demonstrate that eIF4GI and DAP5 specifically bind to the 5' UTRs of these cap-independently translated mRNAs. Surprisingly, we find that the eIF4E binding domain of eIF4GI increases not only the binding affinity, but also the selectivity among these mRNAs. We further demonstrate that the affinities of eIF4GI and DAP5 binding to these 5' UTRs correlate with the efficiency with which these factors drive cap-independent translation of these mRNAs. Integrating the results of our binding and translation assays, we show that eIF4GI and/or DAP5 are critical for recruitment of a specific subset of mRNAs to the ribosome and provide mechanistic insight into their capindependent translation. Running title: eIF4GI or DAP5 drives cap-independent translation initiationKeywords: 5' CITE | IRES | eIF4GI | DAP5 | fluorescence anisotropy

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“…However, under the conditions of impaired canonical cap-dependent translation, cap-independent translation is required for cell survival and stress recovery [32][33][34]. During this process, 40S ribosomes can be directly recruited via an internal ribosome entry site (IRES) element to the 5' untranslated region (UTR) of mRNA [35,36]. IRES trans-acting factors (ITAFs) are necessary for helping to recruit 40S ribosomes to promote translation.…”

Section: Bidirectional Translational Reprogrammingmentioning

confidence: 99%

The role of CSDE1 in translational reprogramming and human diseases

2020

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CSDE1 (cold shock domain containing E1) plays a key role in translational reprogramming, which determines the fate of a number of RNAs during biological processes. Interestingly, the role of CSDE1 is bidirectional. It not only promotes and represses the translation of RNAs but also increases and decreases the abundance of RNAs. However, the mechanisms underlying this phenomenon are still unknown. In this review, we propose a "protein-RNA connector" model to explain this bidirectional role and depict its three versions: sequential connection, mutual connection and facilitating connection. As described in this molecular model, CSDE1 binds to RNAs and cooperates with other protein regulators. CSDE1 connects with different RNAs and their regulators for different purposes. The triple complex of CSDE1, a regulator and an RNA reprograms translation in different directions for each transcript. Meanwhile, a number of recent studies have found important roles for CSDE1 in human diseases. This model will help us to understand the role of CSDE1 in translational reprogramming and human diseases.

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Cap-Independent Translation: What’s in a Name?

Cited by 99 publications

References 94 publications

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

5’ UTR recruitment of eIF4GI or DAP5 drives cap-independent translation for a subset of human mRNAs

The role of CSDE1 in translational reprogramming and human diseases

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Cap-Independent Translation: What’s in a Name?

Cited by 99 publications

References 94 publications

NAD + -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD + -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

5’ UTR recruitment of eIF4GI or DAP5 drives cap-independent translation for a subset of human mRNAs

The role of CSDE1 in translational reprogramming and human diseases

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NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated