Evidence of abundant stop codon readthrough in Drosophila and other Metazoa
Name
Kellis_Evidence of abundant.pdf
Size
3.66 MB
Format
Adobe PDF
Checksum (MD5)
0d0587858f50cd9d51b6bee4c87523c6
Author(s)
Jungreis, Irwin
Lin, Michael F.
Spokony, Rebecca
Chan, Clara Sophia
Negre, Nicolas
Victorsen, Alec
White, Kevin P.
Kellis, Manolis
Date Issued
October 2011
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory Press
Citation
Jungreis, I. et al. “Evidence of Abundant Stop Codon Readthrough in Drosophila and Other Metazoa.” Genome Research 21.12 (2011): 2096–2113. © 2011 by Cold Spring Harbor Laboratory Press
Version
Final published version
Abstract
While translational stop codon readthrough is often used by viral genomes, it has been observed for only a handful of eukaryotic genes. We previously used comparative genomics evidence to recognize protein-coding regions in 12 species of Drosophila and showed that for 149 genes, the open reading frame following the stop codon has a protein-coding conservation signature, hinting that stop codon readthrough might be common in Drosophila. We return to this observation armed with deep RNA sequence data from the modENCODE project, an improved higher-resolution comparative genomics metric for detecting protein-coding regions, comparative sequence information from additional species, and directed experimental evidence. We report an expanded set of 283 readthrough candidates, including 16 double-readthrough candidates; these were manually curated to rule out alternatives such as A-to-I editing, alternative splicing, dicistronic translation, and selenocysteine incorporation. We report experimental evidence of translation using GFP tagging and mass spectrometry for several readthrough regions. We find that the set of readthrough candidates differs from other genes in length, composition, conservation, stop codon context, and in some cases, conserved stem–loops, providing clues about readthrough regulation and potential mechanisms. Lastly, we expand our studies beyond Drosophila and find evidence of abundant readthrough in several other insect species and one crustacean, and several readthrough candidates in nematode and human, suggesting that functionally important translational stop codon readthrough is significantly more prevalent in Metazoa than previously recognized.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Mathematics
Terms of Use
Creative Commons Attribution-NonCommercial 3.0 Unported License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/gr.119974.110
