An Out-of-frame Overlapping Reading Frame in the Ataxin-1 Coding Sequence Encodes a Novel Ataxin-1 Interacting Protein

Bergeron, David Μ.; Lapointe, Catherine; Bissonnette, Cyntia; Tremblay, Guillaume; Motard, Julie; Roucou, Xavier

doi:10.1074/jbc.m113.472654

Cited by 56 publications

(64 citation statements)

References 48 publications

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“…Other than the rat Adora2a gene, only three other dual coding genes containing alternative reading frames have been reported to date (7,8,53). For these three genes, a novel protein product was found to be translated from a transcript that was initially identified for the translation of another protein.…”

Section: Discussionmentioning

confidence: 99%

“…interaction between the PrP and AltPrP proteins has been reported. During the preparation of this manuscript, a new dual coding gene (ATXN1) containing alternative reading frames was reported (53). The newly identified Alt-ATXN1 protein is translated from a downstream AUG (ϩ3 frame) of the ATXN1 gene and functions as a novel interacting protein of the ATXN1 protein.…”

Section: Discussionmentioning

confidence: 99%

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The A2A Adenosine Receptor Is a Dual Coding Gene

Lee¹,

Lai

Lee

et al. 2014

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The A2A Adenosine Receptor Is a Dual Coding Gene

Lee¹,

Lai

Lee

et al. 2014

Journal of Biological Chemistry

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“…Finally, hundreds of unannotated ORFs overlapping a canonical CDS have been described as well (Vanderperre et al 2011(Vanderperre et al , 2013Bergeron et al 2013;Slavoff et al 2013). These ORFs are at the same locus as an annotated CDS but encoded in an alternative reading frame and can either partially overlap the CDS or be completely nested within it.…”

Section: Polycistronic Regions: Overlapping Orfs On One Mrnamentioning

confidence: 99%

“…The now irrefutable existence of "alternative" proteins Recent work has revealed that genomes harbor many nonannotated open reading frames (ORFs) (Vanderperre et al 2011;Bergeron et al 2013;Anderson et al 2015;Mouilleron et al 2016;D'Lima et al 2017;Plaza et al 2017). Although two decades have passed since the first eukaryotic genome was sequenced, assigning translated ORFs to genetic loci remains a daunting task (Basrai et al 1997;Claverie et al 1997;Ladoukakis et al 2011).…”

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confidence: 99%

Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship

et al. 2018

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Technological advances promise unprecedented opportunities for whole exome sequencing and proteomic analyses of populations. Currently, data from genome and exome sequencing or proteomic studies are searched against reference genome annotations. This provides the foundation for research and clinical screening for genetic causes of pathologies. However, current genome annotations substantially underestimate the proteomic information encoded within a gene. Numerous studies have now demonstrated the expression and function of alternative (mainly small, sometimes overlapping) ORFs within mature gene transcripts. This has important consequences for the correlation of phenotypes and genotypes. Most alternative ORFs are not yet annotated because of a lack of evidence, and this absence from databases precludes their detection by standard proteomic methods, such as mass spectrometry. Here, we demonstrate how current approaches tend to overlook alternative ORFs, hindering the discovery of new genetic drivers and fundamental research. We discuss available tools and techniques to improve identification of proteins from alternative ORFs and finally suggest a novel annotation system to permit a more complete representation of the transcriptomic and proteomic information contained within a gene. Given the crucial challenge of distinguishing functional ORFs from random ones, the suggested pipeline emphasizes both experimental data and conservation signatures. The addition of alternative ORFs in databases will render identification less serendipitous and advance the pace of research and genomic knowledge. This review highlights the urgent medical and research need to incorporate alternative ORFs in current genome annotations and thus permit their inclusion in hypotheses and models, which relate phenotypes and genotypes.

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“…Understanding the mechanisms of the translation of oORFs in tumor cells is important in the investigation of tumor immunology. Recent studies have characterised two oPEPs encoded from alternative proteins in human cell lines, AltPrP (Vanderperre et al, 2011) and AltATXN1 (Bergeron et al, 2013). Although only a few dPEPs have been identified, they are found to be translated from dORFs via leaky scanning and ribosomal reinitiation mechanisms or translated as a ribosomal entry site contained on the 3′UTR (Mercer et al, 2011).…”

Section: Opeps/ Dpepsmentioning

confidence: 99%

The characterization of peptides expressed from short open reading frames (sORFs)

Feng¹

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Potentially translatable short open reading frames (sORFs) of less than 100 codons are present on both mRNAs and non-coding RNAs (ncRNAs) and 50% of mammalian mRNAs contain at least one sORF. We hypothesize that a subset of sORFs encode for functional short peptides (sPEPs) that are expressed and contribute to proteome complexity. Our recent bioinformatic studies showed that nearly 2% of sORFs are conserved between several species indicating that these sORFs may have critical functions. Recent proteomic studies have identified over 1,000 sPEPs in human cell lines showing that some sORFs are indeed translated. Surprisingly, a number of peptides have been identified that are encoded by sORFs present in ncRNAs. In order to extend and validate these studies, I extracted low molecular weight proteins from HeLa and HEK293 cell lysates by either SDS-PAGE or ERLIC fractionation. These extracts were digested with trypsin or LysC and analysed by nano LC-MS/MS. The resulting MS/MS data was searched against the UniProKB/Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were searched against the human RefSeq database. ProteinPilot TM was also used to identify sORF-encoded peptides by searching against an in-house sORF and the Human AlternativeOpen Reading Frame (HaltORF) databases. To date, I have identified several sPEPs including three that are novel. These sPEPs have a mass of less than 20 kDa. One of those is expressed from an ncRNA transcript and is expected to be secreted. The other two sPEPs are encoded by upstream open reading frames (uORFs) on mRNA transcripts; one of these is predicted to localise to the cytoplasm while the other is expected to be secreted. The role, if any, of these peptides has yet to be determined but their identification has provided a pool of candidates for further molecular characterization in order to determine their function.3

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An Out-of-frame Overlapping Reading Frame in the Ataxin-1 Coding Sequence Encodes a Novel Ataxin-1 Interacting Protein

Cited by 56 publications

References 48 publications

The A2A Adenosine Receptor Is a Dual Coding Gene

The A2A Adenosine Receptor Is a Dual Coding Gene

Recognition of the polycistronic nature of human genes is critical to understanding the genotype-phenotype relationship

The characterization of peptides expressed from short open reading frames (sORFs)

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