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

Autor: Pedro Patraquim, Emile G. Magny, José I. Pueyo, Ana Isabel Platero, Juan Pablo Couso
Přispěvatelé: Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Andalucía
Rok vydání: 2022
Předmět:
Zdroj: Nature communications. 13(1)
ISSN: 2041-1723
Popis: 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”.
This work was funded by the following grants: PID2019-106227GB-I00 by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación and CEX2020-00108-M Unidad de Excelencia María de Maeztu (J.P.C.); and by a Postdoctoral Fellowship DOC_01144/2020, awarded by the Junta de Andalucía/CSIC (P.P.).
With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-00108-M ).
Databáze: OpenAIRE
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