54
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Differential Use of Signal Peptides and Membrane Domains Is a Common Occurrence in the Protein Output of Transcriptional Units

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Membrane organization describes the orientation of a protein with respect to the membrane and can be determined by the presence, or absence, and organization within the protein sequence of two features: endoplasmic reticulum signal peptides and alpha-helical transmembrane domains. These features allow protein sequences to be classified into one of five membrane organization categories: soluble intracellular proteins, soluble secreted proteins, type I membrane proteins, type II membrane proteins, and multi-spanning membrane proteins. Generation of protein isoforms with variable membrane organizations can change a protein's subcellular localization or association with the membrane. Application of MemO, a membrane organization annotation pipeline, to the FANTOM3 Isoform Protein Sequence mouse protein set revealed that within the 8,032 transcriptional units (TUs) with multiple protein isoforms, 573 had variation in their use of signal peptides, 1,527 had variation in their use of transmembrane domains, and 615 generated protein isoforms from distinct membrane organization classes. The mechanisms underlying these transcript variations were analyzed. While TUs were identified encoding all pairwise combinations of membrane organization categories, the most common was conversion of membrane proteins to soluble proteins. Observed within our high-confidence set were 156 TUs predicted to generate both extracellular soluble and membrane proteins, and 217 TUs generating both intracellular soluble and membrane proteins. The differential use of endoplasmic reticulum signal peptides and transmembrane domains is a common occurrence within the variable protein output of TUs. The generation of protein isoforms that are targeted to multiple subcellular locations represents a major functional consequence of transcript variation within the mouse transcriptome.

          Synopsis

          Many genes produce only a single protein; however, others are known to produce a number of proteins with different functions in the cell. The function of a protein within the cell is influenced by its location; for example, proteins that are secreted can act as messengers, whereas proteins embedded in the membrane may act as receptors or channels. Features that determine the eventual location of a protein are found in the protein sequence. The authors identified two such features, the signal peptide that targets a protein for secretion, and the transmembrane domain that embeds a protein in the membrane, predicting their occurrence in mouse protein sequences. The authors then searched the entire mouse genome for genes that vary in the use of these features in protein isoforms. They found a large number of genes that produce proteins with variation in these features; for example, they identified genes producing proteins that are both secreted and intracellular, and genes producing proteins that are both membrane bound and soluble. This process is likely to be a major source of functional variation in the output of mammalian genes.

          Related collections

          Most cited references54

          • Record: found
          • Abstract: found
          • Article: not found

          Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

          Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Understanding alternative splicing: towards a cellular code.

            In violation of the 'one gene, one polypeptide' rule, alternative splicing allows individual genes to produce multiple protein isoforms - thereby playing a central part in generating complex proteomes. Alternative splicing also has a largely hidden function in quantitative gene control, by targeting RNAs for nonsense-mediated decay. Traditional gene-by-gene investigations of alternative splicing mechanisms are now being complemented by global approaches. These promise to reveal details of the nature and operation of cellular codes that are constituted by combinations of regulatory elements in pre-mRNA substrates and by cellular complements of splicing regulators, which together determine regulated splicing pathways.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A new method for predicting signal sequence cleavage sites.

              A new method for identifying secretory signal sequences and for predicting the site of cleavage between a signal sequence and the mature exported protein is described. The predictive accuracy is estimated to be around 75-80% for both prokaryotic and eukaryotic proteins.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Role: Editor
                Role: Editor
                Role: Editor
                Role: Editor
                Journal
                PLoS Genet
                pgen
                PLoS Genetics
                Public Library of Science (San Francisco, USA )
                1553-7390
                1553-7404
                April 2006
                28 April 2006
                : 2
                : 4
                : e46
                Affiliations
                [1 ] Institute for Molecular Bioscience and ARC Centre in Bioinformatics, University of Queensland, St. Lucia, Queensland, Australia
                [2 ] Advanced Computational Modeling Centre, University of Queensland, St. Lucia, Queensland, Australia
                [3 ] Genome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center, RIKEN Yokohama Institute, Yokohama, Japan
                [4 ] Genome Science Laboratory, Discovery Research Institute, RIKEN Wako Institute, Wako, Japan
                The Jackson Laboratory, US
                MRC-Harwell, UK
                NHGRI-NIH, US
                Lawrence Livermore National Laboratory, US
                The Jackson Laboratory, US
                Author notes
                * To whom correspondence should be addressed. E-mail: R.Teasdale@ 123456imb.uq.edu.au
                Article
                05-PLGE-RA-0230R3 plge-02-04-12
                10.1371/journal.pgen.0020046
                1449889
                16683029
                ff849be2-1265-4307-ade2-a039171fe004
                Copyright: © 2006 Davis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 August 2005
                : 10 February 2006
                Page count
                Pages: 10
                Categories
                Research Article
                Bioinformatics - Computational Biology
                Biotechnology
                Cell Biology
                Evolution
                Genetics/Genomics
                Genetics/Gene Expression
                Mus (Mouse)
                Homo (Human)
                Custom metadata
                Davis MJ, Hanson KA, Clark F, Fink JL, Zhang F, et al. (2006) Differential use of signal peptides and membrane domains is a common occurrence in the protein output of transcriptional units. PLoS Genet 2(4): e46. DOI: 10.1371/journal.pgen.0020046
                Fantom_Logo.jpg

                Genetics
                Genetics

                Comments

                Comment on this article