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Pervasiveness of Microprotein Function Amongst Drosophila Small Open Reading Frames (SMORFS)

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posted on 2024-12-20, 10:32 authored by Ana Isabel Platero, Jose Pueyo-Marques, Sarah Anne Bishop, Emile Gerard Magny, Juan Pablo Couso

Small Open Reading Frames (smORFs) of less than 100 codons remain mostly uncharacterised. About a thousand smORFs per genome encode peptides and microproteins about 70–80 aa long, often containing recognisable protein structures and markers of translation, and these are referred to as short Coding Sequences (sCDSs). The characterisation of individual sCDSs has provided examples of smORFs’ function and conservation, but we cannot infer the functionality of all other metazoan smORFs from these. sCDS function has been characterised at a genome-wide scale in yeast and bacteria, showing that hundreds can produce a phenotype, but attempts in metazoans have been less successful. Either most sCDSs are not functional, or classic experimental techniques do not work with smORFs due to their shortness. Here, we combine extensive proteomics with bioinformatics and genetics in order to detect and corroborate sCDS function in Drosophila. Our studies nearly double the number of sCDSs with detected peptides and microproteins and an experimentally corroborated function. Finally, we observe a correlation between proven sCDS protein function and bioinformatic markers such as conservation and GC content. Our results support that sCDSs peptides and microproteins act as membrane-related regulators of canonical proteins, regulators whose functions are best understood at the cellular level, and whose mutants produce little, if any, overt morphological phenotypes.

History

Publication status

  • Published

File Version

  • Published version

Journal

Cells

ISSN

2073-4409

Publisher

MDPI AG

Issue

24

Volume

13

Article number

2090

Department affiliated with

  • Professional Services Publications
  • BSMS Publications

Institution

University of Sussex

Full text available

  • Yes

Peer reviewed?

  • Yes

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