2019
DOI: 10.1080/15476286.2019.1632634
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uORF-mediated translational control: recently elucidated mechanisms and implications in cancer

Abstract: Protein synthesis is tightly regulated, and its dysregulation can contribute to the pathology of various diseases, including cancer. Increased or selective translation of mRNAs can promote cancer cell proliferation, metastasis and tumor expansion. Translational control is one of the most important means for cells to quickly adapt to environmental stresses. Adaptive translation involves various alternative mechanisms of translation initiation. Upstream open reading frames (uORFs) serve as a major regulator of s… Show more

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Cited by 42 publications
(35 citation statements)
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“…In this context the repression imposed by uORFs on the initiation of translation of the main ORF is relieved, thus allowing the production of specific proteins in response to stress. The mode of action of each uORF appears dictated by its initiation codon context, secondary structure and coding capacities [83,84]. Moreover, the overall regulation of a given mRNA will depend on the specific combination and organisation of uORFs in its 5 terminal region [85].…”
Section: Regulation By Uorfmentioning
confidence: 99%
See 1 more Smart Citation
“…In this context the repression imposed by uORFs on the initiation of translation of the main ORF is relieved, thus allowing the production of specific proteins in response to stress. The mode of action of each uORF appears dictated by its initiation codon context, secondary structure and coding capacities [83,84]. Moreover, the overall regulation of a given mRNA will depend on the specific combination and organisation of uORFs in its 5 terminal region [85].…”
Section: Regulation By Uorfmentioning
confidence: 99%
“…It therefore represents a highly sensitive and responsive mean to regulate specific protein expression under stress conditions. Mutations affecting the activity of uORF and consequently the translation of the downstream ORF have been reported in different cancer models [83]. It is likely that uORFs mutations could as well affect the expression of stress-regulated factors and favour some cancer-associated processes but this has still not been reported to date.…”
Section: Uorfs Translation Upon Er Stressmentioning
confidence: 99%
“…Although there is a correlation between uORF-mediated translational (dys)regulation and tumorigenesis [ 14 , 31 ], our data show that ABCE1 uORF-mediated translational regulation does not seem to contribute to the tumorigenic process in HCT116 cells ( Figure 10 ). Supporting the lack of oncogenic function of the ABCE1 AUG uORFs, both ABCE1 mRNA and protein levels are similar in different colorectal cancer cell lines, as well as in the non-tumorigenic NCM460 cells ( Figure 10 ).…”
Section: Discussionmentioning
confidence: 65%
“…Bioinformatics studies estimate that ~50% to ~60% of human transcripts have at least one uORF [ 9 , 10 ]. Indeed, uORFs are frequently present in transcription factors, cellular receptors, oncogenes, and transcripts with a role in stress response, cell growth, and differentiation control [ 11 , 12 , 13 , 14 ]. uORFs are typically described as repressors of translation initiation at the main coding sequence under normal cellular conditions [ 4 , 9 , 13 ].…”
Section: Introductionmentioning
confidence: 99%
“…However, after birth, the uORF-mediated translational repression of main ORFs did not always occurred, which could be achieved by ribosome bypass or translation re-initiation [37]. The majority (57.9%, 1,719/2,971) of uORFs were found exclusively in a single stage, implying that uORF-mediated translational regulation occurred in a stage-specific manner (Fig.…”
Section: Dynamics Of Translational Efficiency and Contribution Of Regmentioning
confidence: 95%