Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them

Leppek, Kathrin; Das, Rhiju; Barna, Maria

doi:10.1038/nrm.2017.103

Cited by 618 publications

(658 citation statements)

References 205 publications

(264 reference statements)

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“…As 5 0 UTR elements such as RNA secondary structures and upstream open reading frames are known to influence translation, truncations within 5 0 UTR sequences can also affect the translational efficiency or regulation of their mRNAs [26,27]. As 5 0 UTR elements such as RNA secondary structures and upstream open reading frames are known to influence translation, truncations within 5 0 UTR sequences can also affect the translational efficiency or regulation of their mRNAs [26,27].…”

Section: Resultsmentioning

confidence: 99%

mRNA 5′ ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced

2019

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Until cytoplasmic recapping was discovered, decapping was thought to irreversibly destine an mRNA to degradation. Contradicting this idea, we readily observe mRNAs targeted by cytoplasmic capping in uncapped, yet stable forms. 5′ rapid amplification of cDNA ends (RACE) shows that nearly all uncapped ends correspond to capped analysis of gene expression tags and that the recapping of ZNF207 mRNA may be restricted to a single splice isoform. Here, a modified RACE approach detected uncapped 5′ RNA ends mapping to 46 mRNAs in cells expressing a dominant negative cytoplasmic capping enzyme and in normal cells. Eleven of 46 cloned mRNAs also contained splice isoform‐limiting sequences. Collectively, these data reinforce earlier work and suggest that alternative splicing may play a role in targeting transcripts for – and/or determining the position of – cytoplasmic capping.

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Section: Resultsmentioning

confidence: 99%

mRNA 5′ ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced

2019

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“…Additionally, IRESs also aid in the translation of proteins encoded by mRNAs with highly structured 5′ UTRs, where the accessibility of the cap‐binding complex is limited (Fig ). Very nice reviews describing IRES‐mediated translation in detail, including the trans ‐acting factors, have recently been published .…”

Section: Modes Of Translation Initiationmentioning

confidence: 99%

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

2018

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Recent work has brought to light many different mechanisms of translation initiation that function in cells in parallel to canonical cap-dependent initiation. This has important implications for cancer. Canonical cap-dependent translation initiation is inhibited by many stresses such as hypoxia, nutrient limitation, proteotoxic stress, or genotoxic stress. Since cancer cells are often exposed to these stresses, they rely on alternate modes of translation initiation for protein synthesis and cell growth. Cancer mutations are now being identified in components of the translation machinery and in -regulatory elements of mRNAs, which both control translation of cancer-relevant genes. In this review, we provide an overview on the various modes of non-canonical translation initiation, such as leaky scanning, translation re-initiation, ribosome shunting, IRES-dependent translation, and mA-dependent translation, and then discuss the influence of stress on these different modes of translation. Finally, we present examples of how these modes of translation are dysregulated in cancer cells, allowing them to grow, to proliferate, and to survive, thereby highlighting the importance of translational control in cancer.

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“…However, they play a critical role in the regulation of mRNA stability and protein translation via the interaction with RNA-binding proteins (RBPs) [45, 46]. 5′ UTR is an important element for ribosome recruitment and start codon choice [47], and it may have a crucial impact on translation [48]. 3′ UTR determines protein expression levels through the regulation of mRNA stability and translation mediated by AU-rich elements, and also facilitates local translation through the control of mRNA localization [49].…”

Section: Chemical Modification Of Mrnamentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them

Cited by 618 publications

References 205 publications

mRNA 5′ ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced

mRNA 5′ ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced

Translation acrobatics: how cancer cells exploit alternate modes of translational initiation

Biomedical applications of mRNA nanomedicine

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