2014
DOI: 10.1016/j.bbrc.2014.09.085
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Upstream open reading frame in 5′-untranslated region reduces titin mRNA translational efficiency

Abstract: Titin is the largest known protein and a critical determinant of myofibril elasticity and sarcomere structure in striated muscle. Accumulating evidence that mRNA transcripts are post-transcriptionally regulated by specific motifs located in the flanking untranslated regions (UTRs) led us to consider the role of titin 5′-UTR in regulating its translational efficiency. Titin 5′-UTR is highly homologues between human, mouse, and rat, and sequence analysis revealed the presence of a stem-loop and two upstream AUG … Show more

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Cited by 9 publications
(12 citation statements)
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“…Recently Cadar et al . [ 37 ] provide evidence that titin translational efficiency is controlled in part by its 5’-UTR, mainly through a cis -regulatory uORF. Titin is the largest known protein, a critical determinant of myofibril elasticity and sarcomere structure in striated muscle.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Recently Cadar et al . [ 37 ] provide evidence that titin translational efficiency is controlled in part by its 5’-UTR, mainly through a cis -regulatory uORF. Titin is the largest known protein, a critical determinant of myofibril elasticity and sarcomere structure in striated muscle.…”
Section: Discussionmentioning
confidence: 99%
“…Cadar et al . [ 37 ] hypothesize that the uORF plays a role in fine tuning mRNA translation by serving as a passive brake to prevent overproduction and hence the wasting of cellular resources, given that the synthesis of this mega-protein is energetically costly.…”
Section: Discussionmentioning
confidence: 99%
“…It was demonstrated that TNN is prone to significant modifications via thiol oxidation during aging, leading to cardiomyopathies (for details see [121]). To understand whether TTN expression can be controlled by uORFs, Cadar and co-authors investigated the 5 UTR of TTN and identified two uORFs that suppressed TTN translation in non-stressed cardiac HL-1 cell line and primary neonatal rat ventricular myocytes [122]. Interestingly, TTN uORFs responded differently to distinct oxidative stressors: doxorubicin [123], but not H 2 O 2 , increased TTN-uORF-mediated translation efficiency [122], suggesting the possibility of various response mechanisms of cardiac cells to ROS.…”
Section: Uorfmentioning
confidence: 99%
“…The 5′-UTR of titin is highly conserved among human, mouse, and rat and contains a stem-loop structure and two upstream AUG codons (uAUGs) converging on a shared in-frame stop codon. Using a luciferase reporter construct containing the 5′-UTR sequence of titin, Cadar et al ( 24 ) showed that the translation efficiency mediated by this 5′-UTR sequence was reduced in cardiomyocytes unless both uAUG sequences were mutated. Furthermore, treatment of cardiomyocytes with doxorubicin-induced stress reduced titin 5′-UTR-mediated translation suppression in cardiomyocytes ( 24 ).…”
Section: Mrna Translation and Degradation In Heartmentioning
confidence: 99%
“…Using a luciferase reporter construct containing the 5′-UTR sequence of titin, Cadar et al ( 24 ) showed that the translation efficiency mediated by this 5′-UTR sequence was reduced in cardiomyocytes unless both uAUG sequences were mutated. Furthermore, treatment of cardiomyocytes with doxorubicin-induced stress reduced titin 5′-UTR-mediated translation suppression in cardiomyocytes ( 24 ). However, the physiological significance of such regulation remains to be demonstrated.…”
Section: Mrna Translation and Degradation In Heartmentioning
confidence: 99%