Shedding Light on the Ghost Proteome
Tristan Cardon1, Isabelle Fournier2, Michel Salzet2
1Laboratoire Protéomique, Réponse Inflammatoire Spectrométrie de Masse (PRISM), Inserm U1192, University of Lille, CHU Lille, F-59000 Lille, France.
Abstract:
Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to the identification of proteins translated from alternative open reading frames (AltORFs) in mRNAs. AltORFs are found in addition to predicted reference ORFs and noncoding RNA. Alternative proteins are not represented in the conventional protein databases, and this 'Ghost proteome' was not considered until recently. Some of these proteins are functional, and there is growing evidence that they are involved in central functions in physiological and physiopathological contexts. Here, we review how this Ghost proteome fills the gap in our understanding of signaling pathways, establishes new markers of pathologies, and highlights therapeutic targets.
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Area of Science:
- Molecular Biology
- Proteomics
- Genomics
Background:
- Eukaryotic messenger RNAs (mRNAs) were traditionally considered monocistronic, encoding only one protein.
- Recent large-scale proteomics studies reveal proteins translated from alternative open reading frames (AltORFs) within mRNAs.
- These alternative proteins, part of the 'Ghost proteome', were previously overlooked and are absent from conventional protein databases.
Purpose of the Study:
- To review the emerging understanding of the 'Ghost proteome' derived from alternative open reading frames (AltORFs).
- To highlight the functional significance and implications of these alternative proteins in biological processes.
- To discuss the potential of the Ghost proteome in identifying novel biomarkers and therapeutic targets.
Main Methods:
- Literature review of recent proteomics and genomics studies.
- Analysis of data identifying alternative open reading frames (AltORFs) in eukaryotic mRNAs.
- Synthesis of evidence regarding the functional roles of the 'Ghost proteome'.
Main Results:
- Identification of a significant 'Ghost proteome' translated from alternative open reading frames (AltORFs).
- Growing evidence supports the functional roles of these alternative proteins in physiological and physiopathological conditions.
- The Ghost proteome offers new insights into cellular signaling pathways.
Conclusions:
- The 'Ghost proteome' represents a significant expansion of the known proteome, challenging the monocistronic mRNA paradigm.
- Alternative proteins encoded by AltORFs are implicated in fundamental biological functions and disease states.
- Understanding the Ghost proteome opens avenues for novel diagnostic markers and therapeutic strategies.
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