| http://purl.uniprot.org/citations/25264194 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25264194 | http://www.w3.org/2000/01/rdf-schema#comment | "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 homologous between human, mouse, and rat, and sequence analysis revealed the presence of a stem-loop and two upstream AUG codons (uAUGs) converging on a shared in frame stop codon. We generated a mouse titin 5'-UTR luciferase reporter construct and targeted the stem-loop and each uAUG for mutation. The wild-type and mutated constructs were transfected into the cardiac HL-1 cell line and primary neonatal rat ventricular myocytes (NRVM). SV40 driven 5'-UTR luciferase activity was significantly suppressed by wild-type titin 5'-UTR (∼ 70% in HL-1 cells and ∼ 60% in NRVM). Mutating both uAUGs was found to alleviate titin 5'-UTR suppression, while eliminating the stem-loop had no effect. Treatment with various growth stimuli: pacing, PMA or neuregulin had no effect on titin 5'-UTR luciferase activity. Doxorubicin stress stimuli reduced titin 5'-UTR suppression, while H2O2 had no effect. A reported single nucleotide polymorphism (SNP) rs13422986 at position -4 of the uAUG2 was introduced and found to further repress titin 5'-UTR luciferase activity. We conclude that the uAUG motifs in titin 5'-UTR serve as translational repressors in the control of titin gene expression, and that mutations/SNPs of the uAUGs or doxorubicin stress could alter titin translational efficiency."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbrc.2014.09.085"xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/author | "Zhong L."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/author | "Lin A."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/author | "Lim C.C."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/author | "Cadar A.G."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/author | "Valenzuela M.O."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/name | "Biochem Biophys Res Commun"xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/pages | "185-191"xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/title | "Upstream open reading frame in 5'-untranslated region reduces titin mRNA translational efficiency."xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://purl.uniprot.org/core/volume | "453"xsd:string |
| http://purl.uniprot.org/citations/25264194 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25264194 |
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