Alternative proteins are functional regulators in cell reprogramming by PKA activation

Cardon, Tristan; Franck, Julien; Coyaud, Étienne; Laurent, Estelle; D’Amato, Marina; Maffia, Michele; Vergara, Daniele; Fournier, Isabelle; Salzet, Michel

doi:10.1093/nar/gkaa277

Cited by 26 publications

(26 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as only 40% of lncRNA-encoded micropeptides are longer than 10 aa, many remain undetected [33]. Although graded MS can detect more putative micropeptides, it uses a reference database, which thus limits its ability to predict novel micropeptides [34]. Therefore, Cardon et al [34] exploited a large-scale and unsupervised method based on cross-linking MS followed by shotgun proteomics to gather information on the functional role of novel isoforms and novel proteins (AltProts), mapping them with known pathways by identifying their reference protein (RefProts) interactors.…”

Section: Experimental Verification Of Peptidesmentioning

confidence: 99%

Emerging role of long noncoding RNA-encoded micropeptides in cancer

Ye¹,

Zhang²,

Wang³

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play various important roles in the development of cancers. The widespread applications of ribosome profiling and ribosome nascent chain complex sequencing revealed that some short open reading frames of lncRNAs have micropeptide-coding potential. The resulting micropeptides have been shown to participate in N6-methyladenosine modification, tumor angiogenesis, cancer metabolism, and signal transduction. This review summarizes current information regarding the reported roles of lncRNA-encoded micropeptides in cancer, and explores the potential clinical value of these micropeptides in the development of anti-cancer drugs and prognostic tumor biomarkers.

show abstract

Section: Experimental Verification Of Peptidesmentioning

confidence: 99%

Emerging role of long noncoding RNA-encoded micropeptides in cancer

Ye¹,

Zhang²,

Wang³

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…Finally, identified AltProts are found to be translated, either from mRNA including from the non-coding 5′ & 3′ UTR or a frame shift (+1 or 2 nucleotides) in the CDS of the RefProt, or from ncRNA [ 9 ]. Overall, large-scale bottom-up [ 9 , 10 , 11 , 12 ] and top-down [ 13 , 14 ] proteomics have enable the identification of an important number of these AltProts. Very importantly, AltProts were also shown to be functional and carrying important cell functions [ 12 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Since the study of glioma cell line (NCH82) under activation by a protein kinase A activator, inducing a cellular phenotypic change has confirmed the presence of AltProts in the signaling pathways of protein translation. AltProts were also shown interacting with cytoskeleton proteins (e.g., AltTRNAU1AP, AltMAP2, and AltEPHA5 interacting with TPM4) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-Cov-2 Interactome with Human Ghost Proteome: A Neglected World Encompassing a Wealth of Biological Data

Cardon

Fournier

2020

Microorganisms

Self Cite

View full text Add to dashboard Cite

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics have led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) 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 context. Based on our experience with AltProts, we were interested in finding out their interaction with the viral protein coming from the SARS-CoV-2 virus, responsible for the 2020 COVID-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by affinity purification in co-immunoprecipitation (co-IP) in the perspective of drug repurposing. The initial work revealed the interaction between 332 human cellular reference proteins (RefProts) with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study), plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the ghost proteome for discovering new therapeutic targets, and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.

show abstract

“…Finally, identified AltProts are found to be translated, either from mRNA including from the non-coding 5′ & 3′ UTR or a frame shift (+1 or 2 nucleotides) in the CDS of the RefProt, or from non-coding RNA (ncRNA) [9]. Overall, largescale bottom-up [9][10][11][12] and top-down [13,14] proteomics have enable the identification of an important number of these AltProts. Very importantly, AltProts were also shown to be functional and carrying important cell functions [12,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…AltProts were also shown interacting with cytoskeleton proteins (e.g. AltTRNAU1AP, AltMAP2 and AltEPHA5 interacting with TPM4) [10]. Based on our experience with AltProts we have got interested in finding out their involvement in development of the SARS-CoV-2 virus, responsible for the 2020 Covid-19 outbreak.…”

Section: Introductionmentioning

confidence: 99%

SARS-Cov-2 Interactome with Human Ghost Proteome: A Neglected World Encompassing a Wealth of Biological Data

Cardon¹,

Fournier²,

Salzet³

2020

Preprint

Self Cite

View full text Add to dashboard Cite

Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics has led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) 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 context. Based on our experience with AltProts we have got interested in finding out their involvement in development of the SARS-CoV-2 virus, responsible for the 2020 Covid-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by co-IP in the perspective of drug repurposing. The initial work has revealed the interaction between 332 human cellular RefProts with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study) plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the Ghost proteome for discovering new therapeutic targets and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.

show abstract

Alternative proteins are functional regulators in cell reprogramming by PKA activation

Cited by 26 publications

References 75 publications

Emerging role of long noncoding RNA-encoded micropeptides in cancer

Emerging role of long noncoding RNA-encoded micropeptides in cancer

SARS-Cov-2 Interactome with Human Ghost Proteome: A Neglected World Encompassing a Wealth of Biological Data

SARS-Cov-2 Interactome with Human Ghost Proteome: A Neglected World Encompassing a Wealth of Biological Data

Contact Info

Product

Resources

About