PL EN


Preferences help
enabled [disable] Abstract
Number of results
2015 | 62 | 1 | 57-61
Article title

Potential protein activity modifications of amino acid variants in the human transcriptome

Content
Title variants
Languages of publication
EN
Abstracts
EN
Background: The occurrence of widespread RNA and DNA sequence differences in the human transcriptome was reported in 2011. Similar findings were described in a second independent publication on personal omics profiling investigating the occurrence of dynamic molecular and related medical phenotypes. The suggestion that the RNA sequence variation was likely to affect disease susceptibility prompted us to investigate with a range of algorithms the amino acid variants reported to be present in the identified peptides to determine if they might be disease-causing. Results: The predictive qualities of the different algorithms were first evaluated by using nonsynonymous single-base nucleotide polymorphism (nsSNP) datasets, using independently established data on amino acid variants in several proteins as well as data obtained by mutational mapping and modelling of binding sites in the human serotonin transporter protein (hSERT). Validation of the used predictive algorithms was at a 75% level. Using the same algorithms, we found that widespread RNA and DNA sequence differences were predicted to impair the function of the peptides in over 57% of cases. Conclusions: Our findings suggest that a proportion of edited RNAs which serve as templates for protein synthesis is likely to modify protein function, possibly as an adaptive survival mechanism in response to environmental modifications.
Keywords
Publisher

Year
Volume
62
Issue
1
Pages
57-61
Physical description
Dates
published
2015
received
2014-04-23
revised
2014-10-21
accepted
2014-12-12
online
2015-02-04
Contributors
author
  • Data Mining Group, Institute of Automatic Control, Faculty of Automatic, Electronic and Computer Science, Silesian University of Technology, Gliwice, Poland
author
  • Public Health England, Chilton, Didcot, United Kingdom
  • Public Health England, Chilton, Didcot, United Kingdom
  • Public Health England, Chilton, Didcot, United Kingdom
References
  • Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicticting damaging missense mutations. Nat Methods 7: 248-249.
  • Allali-Hassani A, Wasney GA, Chau I, Hong BS, Senisterra G, Loppnau P, Shi Z, Moult J, Edwards AM, Arrowsmith CH, Park HW, Schapira M, Vedadi M (2009) A survey of proteins encoded by non-synonymous single nucleotide polymorphisms reveals a significant fraction with altered stability and activity. Biochem J 424: 15-26.
  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215: 403-410.
  • Andersen J, Olsen L, Hansen KB, Taboureau O, Jørgensen FS, Jørgensen AM, Bang-Andersen B, Egebjerg J, Strømgaard K, Kristensen AS (2010) Mutational mapping and modeling of the binding site for [S]-citalopram in the human serotonin transporter. J Biol Chem 285: 2051-2063.
  • Bromberg Y, Yachdav G, Rost B (2008) SNAP predicts effect of mutations on protein function. Bioinformatics 24: 2397-2398.
  • Capriotti E, Calabrese R, Casadio R (2006) Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information. Bioinformatics 22: 2729-2734.
  • Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HY, Chen R, Miriami E, Karczewski KJ, Hariharan M, Dewey FE, Cheng Y, Clark MJ, Im H, Habegger L, Balasubramanian S, O'Huallachain M, Dudley JT, Hillenmeyer S, Haraksingh R, Sharon D, Euskirchen G, Lacroute P, Bettinger K, Boyle AP, Kasowski M, Grubert F, Seki S, Garcia M, Whirl-Carrillo M, Gallardo M, Blasco MA, Greenberg PL, Snyder P, Klein TE, Altman RB, Butte AJ, Ashley EA, Gerstein M, Nadeau KC, Tang H, Snyder M (2012) Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148: 1293-1307.
  • Hicks S, Wheeler DA, Plon SE, Kimmel M (2011) Prediction of missense mutation functionality depends on both algorithm and sequence alignment employed. Hum Mutat 32: 661-668.
  • Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4: 1073-1083.
  • Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG (2011) Widespread RNA and DNA sequence differences in the human transcriptome. Science 333: 53-58.
  • Li M, Wang IX, Cheung VG (2012) Response to comments on 'Widespread RNA and DNA sequence differences in the human transcriptome'. Science 335: 1302.
  • Marcucci R, Brindle J, Paro S, Casadio A, Hempel S, Morrice N, Bisso A, Keegan LP, Del Sal G, O'Connell MA (2011) Pin1 and WWP2 regulate GluR2 Q/R site RNA editing by ADAR2 with opposing effects. EMBO J 30: 4211-422.
  • Mi H, Guo N, Kejariwal A, Thomas PD (2007) PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways. Nucleic Acids Res 35: D247-D252.
  • Patnala R, Clements J, Batra J (2013) Candidate gene association studies: a comprehensive guide to useful in silico tools. BMC Genetics 14: 39.
  • Pickrell JK, Gilad Y, Pritchard JK (2012) Comment on 'Widespread RNA and DNA sequence differences in the human transcriptome'. Science 335: 1302.
  • Worth CL, Bickerton GR, Schreyer A, Forman JR, Cheng TM, Lee S, Gong S, Burke DF, Blundell TL (2007) A structural bioinformatics approach to the analysis of nonsynonymous single nucleotide polymorphisms [nsSNPs] and their relation to disease. J Bioinform Comput Biol 5: 1297-1238.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv62p57kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.