No country for old methods: New tools for studying microproteins

Valdivia-Francia, Fabiola; Sendoel, Ataman

doi:10.1016/j.isci.2024.108972

Cited by 9 publications

(1 citation statement)

References 151 publications

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“…The translation of non-canonical proteins from unannotated ORFs is receiving increasing attention (Ingolia et al, 2019;Hassel et al, 2023;Mohsen et al, 2023;Valdivia-Francia & Sendoel, 2024). Not only does this translation appear to be pervasive, involving several thousands of ORFs from yeast to humans, but it also implies that some mRNAs are multicoding, a property not usually associated with eukaryotic mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Non-canonical altPIDD1 protein: unveiling the true major translational output of thePIDD1gene

Comtois,

Jacques,

Métayer

et al. 2024

Preprint

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Proteogenomics has enabled the detection of novel proteins encoded in non-canonical or alternative open reading frames (altORFs) in genes already coding a reference protein. Reanalysis of proteomic and ribo-seq data revealed that the p53-induced death domain-containing protein (orPIDD1) gene encodes a second 171 amino acid protein, altPIDD1, in addition to the known 910 amino acid-long PIDD1 protein. The two ORFs overlap almost completely, and the translation initiation site of altPIDD1 is located upstream of PIDD1. AltPIDD1 has more translational and protein level evidence than PIDD1 across various cell lines and tissues. In HEK293 cells, the altPIDD1 to PIDD1 ratio is 40 to 1, as measured with isotope-labeled (heavy) peptides and targeted proteomics. AltPIDD1 localizes to cytoskeletal structures labeled with phalloidin, including stress fibres, lamellipodia and filopodia, interacts with cytoskeletal proteins and is cleaved during apoptosis. Unlike most non-canonical proteins, altPIDD1 is not evolutionarily young but emerged in placental mammals. Overall, we identifyPIDD1as a dual-coding gene, with altPIDD1, not the annotated protein, being the primary product of translation.Summary blurbThis research uncoversPIDD1as a dual-coding gene, revealing a previously unknown protein, altPIDD1, as the primary product with higher expression and cytoskeletal interactions.

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Section: Discussionmentioning

confidence: 99%