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Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data

Edwards, YJK; Lobley, AE; Pentony, MM; Jones, DT; (2009) Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data. Genome Biology , 10 (5) , Article R50. 10.1186/gb-2009-10-5-r50. Green open access

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Abstract

Background: Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins.Results: In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed.Conclusions: Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function.

Type: Article
Title: Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/gb-2009-10-5-r50
Publisher version: http://dx.doi.org/10.1186/gb-2009-10-5-r50
Language: English
Additional information: © 2009 Edwards et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Ubiquitin-proteasome system, Natively unfolded proteins, Alga chlamydomonas-reinhardtii, Microrna target predictions, Unstructured proteins, Functional anthology, Structural disorder, Posttranslational modifications, Transcriptional activation, Cardiac dysfunction
UCL classification: UCL > School of BEAMS > Faculty of Engineering Science > Computer Science
URI: http://discovery.ucl.ac.uk/id/eprint/103177
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