Most cited article - PubMed ID 31234415
Functionally Significant Features in the 5' Untranslated Region of the ABCA1 Gene and Their Comparison in Vertebrates
The 12 members of the ABCA subfamily in humans are known for their ability to transport cholesterol and its derivatives, vitamins, and xenobiotics across biomembranes. Several ABCA genes are causatively linked to inborn diseases, and the role in cancer progression and metastasis is studied intensively. The regulation of translation initiation is implicated as the major mechanism in the processes of post-transcriptional modifications determining final protein levels. In the current bioinformatics study, we mapped the features of the 5' untranslated regions (5'UTR) known to have the potential to regulate translation, such as the length of 5'UTRs, upstream ATG codons, upstream open-reading frames, introns, RNA G-quadruplex-forming sequences, stem loops, and Kozak consensus motifs, in the DNA sequences of all members of the subfamily. Subsequently, the conservation of the features, correlations among them, ribosome profiling data as well as protein levels in normal human tissues were examined. The 5'UTRs of ABCA genes contain above-average numbers of upstream ATGs, open-reading frames and introns, as well as conserved ones, and these elements probably play important biological roles in this subfamily, unlike RG4s. Although we found significant correlations among the features, we did not find any correlation between the numbers of 5'UTR features and protein tissue distribution and expression scores. We showed the existence of single nucleotide variants in relation to the 5'UTR features experimentally in a cohort of 105 breast cancer patients. 5'UTR features presumably prepare a complex playground, in which the other elements such as RNA binding proteins and non-coding RNAs play the major role in the fine-tuning of protein expression.
- Keywords
- 5′ untranslated region, ABC transporters, ABCA subfamily, bioinformatics, cis-acting elements,
- MeSH
- 5' Untranslated Regions genetics MeSH
- ATP Binding Cassette Transporter, Subfamily A classification genetics metabolism MeSH
- Biological Transport genetics MeSH
- Cholesterol metabolism MeSH
- Introns genetics MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Multigene Family genetics MeSH
- Open Reading Frames genetics MeSH
- Protein Biosynthesis genetics MeSH
- Ribosomes genetics metabolism MeSH
- Computational Biology MeSH
- Xenobiotics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 5' Untranslated Regions MeSH
- ATP Binding Cassette Transporter, Subfamily A MeSH
- Cholesterol MeSH
- Xenobiotics MeSH