title: Computational analysis of translational readthrough proteins in Drosophila and yeast reveals parallels to alternative splicing.
abstract: In translational readthrough (TR) the ribosome continues extending the nascent protein beyond the first in-frame termination codon. Due to the lack of dedicated analyses of eukaryotic TR cases, the associated functional-evolutionary advantages are still unclear. Here, based on a variety of computational methods, we describe the structural and functional properties of previously proposed D. melanogaster and S. cerevisiae TR proteins and extensions. We found that in D. melanogaster TR affects long proteins in mainly regulatory roles. Their TR-extensions are structurally disordered and rich in binding motifs, which, together with their cell-type- and developmental stage-dependent inclusion, suggest that similarly to alternatively spliced exons they rewire cellular interaction networks in a temporally and spatially controlled manner. In contrast, yeast TR proteins are rather short and fulfil mainly housekeeping functions, like translation. Yeast extensions usually lack disorder and linear motifs, which precludes elucidating their functional relevance with sufficient confidence. Therefore we propose that by being much more restricted and by lacking clear functional hallmarks in yeast as opposed to fruit fly, TR shows remarkable parallels with alternative splicing. Additionally, the lack of conservation of TR extensions among orthologous TR proteins suggests that TR-mediated functions may be generally specific to lower taxonomic levels.
authors: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium.
authors: Rita
authors: R
authors: Pancsa
authors: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium.
authors: Mauricio
authors: M
authors: Macossay-Castillo
authors: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium.
authors: Simone
authors: S
authors: Kosol
authors: Flanders Institute for Biotechnology (VIB), Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Pleinlaan 2, Brussels, Belgium.|Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, 1117 Budapest, Hungary.
authors: Peter
authors: P
authors: Tompa
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D003198:Computer Simulation; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D008954:Models, Biological; D014176:Protein Biosynthesis / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D029701:Saccharomyces cerevisiae Proteins