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Translation and natural selection of micropeptides from long non-canonical RNAs

Author

Listed:
  • Pedro Patraquim

    (CSIC-UPO)

  • Emile G. Magny

    (CSIC-UPO)

  • José I. Pueyo

    (Brighton and Sussex Medical School)

  • Ana Isabel Platero

    (CSIC-UPO)

  • Juan Pablo Couso

    (CSIC-UPO)

Abstract

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to rely only on RNA expression, sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For the latter, we develop a bioinformatics pipeline to detect small ORF homologues, and reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA biochemical functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them “long non-canonical RNAs”.

Suggested Citation

  • Pedro Patraquim & Emile G. Magny & José I. Pueyo & Ana Isabel Platero & Juan Pablo Couso, 2022. "Translation and natural selection of micropeptides from long non-canonical RNAs," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34094-y
    DOI: 10.1038/s41467-022-34094-y
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    References listed on IDEAS

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    3. Dominique Lauressergues & Jean-Malo Couzigou & Hélène San Clemente & Yves Martinez & Christophe Dunand & Guillaume Bécard & Jean-Philippe Combier, 2015. "Primary transcripts of microRNAs encode regulatory peptides," Nature, Nature, vol. 520(7545), pages 90-93, April.
    4. William R. Blevins & Jorge Ruiz-Orera & Xavier Messeguer & Bernat Blasco-Moreno & José Luis Villanueva-Cañas & Lorena Espinar & Juana Díez & Lucas B. Carey & M. Mar Albà, 2021. "Uncovering de novo gene birth in yeast using deep transcriptomics," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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    Cited by:

    1. Bharat Ravi Iyengar & Anna Grandchamp & Erich Bornberg-Bauer, 2024. "How antisense transcripts can evolve to encode novel proteins," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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