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Small open reading frame-encoded protein production is modulated by nonsense-mediated decay in breast cancer

ABSTRACT: Small open reading frame-encoded protein production is modulated by nonsense-mediated decay in breast cancer

PROVIDER: PRJEB61453 | ENA |

REPOSITORIES: ENA

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MOTS-c: A Novel Peptide Encoded by a Short Mitochondrial Open Reading Frame Regulates Metabolic Homeostasis

Project description:Mitochondria are known to be functional organelles, but their role as a signaling unit is increasingly being appreciated. The recent identification of a short open reading frame (sORF) in the mitochondrial DNA (mtDNA) that encodes a signaling peptide, humanin, suggests the possible existence of additional sORFs in the mtDNA that yield bioactive peptides. Here we report the identification of a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA -c) that regulates insulin sensitivity and metabolic homeostasis. MOTS-c is detected in various tissues and in circulation in an age-dependent manner. Its primary target organ appears to be the skeletal muscle and its cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, causing a significant accumulation of AICAR levels concomitantly with AMPK activation. MOTS-c treatment in mice prevented age-dependent and high-fat diet-induced insulin resistance, as well as diet-induced obesity. These results suggest that mitochondria may be more actively engaged in regulating metabolic homeostasis than previously recognized, through the production of peptides encoded within its genome that act at the cellular and organismal level. Human embryonic kidney cells (HEK293 cell line) were cultured in 10-cm dishes in 7 mL of phenol-free DMEM supplemented with 10% FBS and incubated with water (controls) or the 16-amino-acid peptide mitochondrial open-reading-frame of the twelve S rRNA-c (MOTS-c, 10 uM) for 4 or 72 hours prior to RNA extraction.

2015-03-07 | E-GEOD-65068 | biostudies-arrayexpress

Small open reading frame-encoded protein production is modulated by nonsense-mediated decay in breast cancer

Project description:Peptides from low abundance non-canonical proteins encoded by the human genome are presented by the major histocompatibility complex and serve as potential neoantigens or therapeutic targets. However, their prevalence in the genome is unclear. We identified several non-canonical proteins produced by breast cancer cell lines using proteogenomics approach. Although these proteins were detectable, the transcripts and corresponding proteins showed low abundance and inconsistent expression pattern. Targeting the nonsense-mediated decay pathway by UPF1-knockdown increased the levels of both non-coding transcripts and non-canonical proteins, suggesting they are subjected to degradation by conserved quality control mechanisms in cells. We also observed increased expression of unannotated transcripts and human leukocyte antigen transcripts associated with antigen presentation. These observations suggest that UPF1 has a role in regulating or suppressing transcriptional noise and that modulating the expression level of UPF1 could expand the reservoir of neoantigens and increase neoantigen presentation, potentially augmenting immunotherapeutic responses in cancers.

2024-01-28 | PXD041585 | Pride

MOTS-c: A Novel Peptide Encoded by a Short Mitochondrial Open Reading Frame Regulates Metabolic Homeostasis

2015-03-07 | GSE65068 | GEO

A coding sequence-embedded principle governs translational reading frame fidelity

Project description:Upon initiation at an AUG start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. Although some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known how the ribosome normally prevents spontaneous frameshift errors. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3’ end of 18S rRNA to scan the AUG-like codons after the decoding process. The internal mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a post-decoding mechanism to safeguard the ribosome in the correct reading frame. Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors. Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes codon “stickiness”. Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes by minimizing the appearance of AUG-like codons in the frame 2. These results suggest an important layer of information embedded within the protein coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.

2016-04-12 | GSE80156 | GEO

Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo

Project description:Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo

| PRJNA790822 | ENA

Identification of small open reading frame encoded peptides of Picosynechococcus sp. PCC 7002 (7002)

Project description:Identification of small open reading frame encoded peptides of Picosynechococcus sp. PCC 7002 (7002)

2025-01-10 | PXD059623 |

Identification of small open reading frame encoded peptides of Thermosynechococcus vestitus BP-1(2133)

Project description:Identification of small open reading frame encoded peptides of Thermosynechococcus vestitus BP-1(2133)

2025-01-09 | PXD059620 |

Identification of small open reading frame encoded peptides of Synechocystis sp. PCC 6803 (6803)

Project description:Identification of small open reading frame encoded peptides of Synechocystis sp. PCC 6803 (6803)

2025-01-08 | PXD059576 |

Identification of small open reading frame encoded peptides of Nostoc sp. PCC 7120 (7120)

Project description:Identification of small open reading frame encoded peptides of Nostoc sp. PCC 7120 (7120)

2025-01-09 | PXD059618 |

Identification of small open reading frame encoded peptides of Synechococcus elongatus PCC 7942 = FACHB-805

Project description:identification of small open reading frame encoded peptides of Synechococcus elongatus PCC 7942 = FACHB-805

2025-01-08 | PXD059575 |

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