Using the sORFs.Org Database

Olexiouk, Volodimir; Menschaert, Gerben

doi:10.1002/cpbi.68

Cited by 10 publications

(4 citation statements)

References 20 publications

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“…Methods sORF selection criteria. sORF-encoded peptides (SEPs) were filtered using ribosome profiling-based metrics derived from sORFs.org, adapting the guidelines from Olexiouk et al 45 . In all, 2343 human SEPs encoded by annotated short CDS genes, lincRNAs, upstream ORFs (uORFs), and intergenic ORFs that passed ribosome sequencing quality thresholds were selected for mitochondrial prediction (Ensembl annotation bundle v92 is applied).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

et al. 2020

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The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution. Here, we show that the mitochondrial proteome, particularly the respiratory chain, is enriched for small proteins. Using a prediction and validation pipeline for SEPs, we report the discovery of 16 endogenous nuclear encoded, mitochondrial-localized SEPs (mito-SEPs). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN, a 71 a.a. peptide encoded by C12orf73, is essential for respiratory chain complex III (CIII) assembly. In human cells, BRAWNIN is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In zebrafish, Brawnin deletion causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BRAWNIN is essential for vertebrate oxidative phosphorylation. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

et al. 2020

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“…These nORFs are pervasive throughout the genome and are observed in both the coding and non coding regions 1,7 . They are variously classified as small ORFs (sORFs) 8,9 which are 1-100 amino acids in length, altORFs 10 , which are proteins in alternate frames to known proteins, Denovogenes 11 or Orphan genes 12 , Pseudogenes 1,13 , and many ncRNAs have been shown to have coding potential [14][15][16][17][18] . These new discoveries challenge traditionally held conservative definitions of ORF, as used until the recent past 19 .…”

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confidence: 99%

Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations

Jagannathan

Meena

Bhayankaram

et al. 2019

Preprint

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Recent advances in proteogenomics indicate that protein or protein-like products can be encoded by previously uncharacterized Open Reading Frames (ORFs) that we define as Novel Open Reading Frames (nORFs) 1 , 2 . Although it is yet unclear if these protein or protein-like products could possess any significant biological function hopes have been raised to target them for anticancer and antimicrobial therapy 3,4 . In this study, we used computational tools to systematically investigate these novel protein sequences for their propensities toward structural disorder, post-translational modifications (PTM) and mutational densities. We found that these novel proteins have significantly higher disorder and similar PTM frequencies compared to known proteins. Although these regions were found to harbour deleterious mutations, we did not observe any correlation between the pathogenicity of mutations and their location (ordered/disordered) within these novel proteins. This study suggests that these nORFs encode an important class of proteins, that could undergo sequence, structural or regulatory changes during complex diseases, and hence warrant further study. Significance:Certain noncoding regions of the genome are known to make protein-like products. These protein-like products have significantly expanded the number of the cellular proteome but we dont know whether they are capable of performing biological functions. Here in this study, we have investigated all such putative protein-like products and analyzed whether they can form structures, whether hey harbour mutations, and whether they can be regulated by biochemical regulatory processes. Results from this study indicate that indeed these protein-like proteins can perform and be involved in all the above processes.

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“…DeepCPP 47 is an exception with superior performance on sORF detection. sORFs.org 63 is a database containing sORF information from ribosome profiling across six species. OpenProt 64 is an ORF prediction resource based on Ribo-seq datasets and MS datasets, and it also can predict sORF by annotating non-AUG initiating codons.…”

Section: Filtration Of Assembled Transcriptsmentioning

confidence: 99%