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Comprehensive identification and characterization of conserved small ORFs in animals

Item Type:Preprint
Title:Comprehensive identification and characterization of conserved small ORFs in animals
Creators Name:Mackowiak, S.D. and Zauber, H. and Bielow, C. and Thiel, D. and Kutz, K. and Calviello, L. and Mastrobuoni, G. and Rajewsky, N. and Kempa, S. and Selbach, M. and Obermayer, B.
Abstract:There is increasing evidence that non-annotated short open reading frames (sORFs) can encode functional micropeptides, but computational identification remains challenging. We expand our published method and predict conserved sORFs in human, mouse, zebrafish, fruit fly and the nematode C. elegans. Isolating specific conservation signatures indicative of purifying selection on encoded amino acid sequence, we identify about 2000 novel sORFs in the untranslated regions of canonical mRNAs or on transcripts annotated as non-coding. Predicted sORFs show stronger conservation signatures than those identified in previous studies and are sometimes conserved over large evolutionary distances. Encoded peptides have little homology to known proteins and are enriched in disordered regions and short interaction motifs. Published ribosome profiling data indicate translation for more than 100 of novel sORFs, and mass spectrometry data gives peptidomic evidence for more than 70 novel candidates. We thus provide a catalog of conserved micropeptides for functional validation in vivo.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:017772
Date:9 April 2015
Official Publication:https://doi.org/10.1101/017772
Related to:
https://edoc.mdc-berlin.de/15045/Final version

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