PXD047963-1

PXD047963 is an original dataset announced via ProteomeXchange.

Title	ROSALIND protects the mitochondrial translational machinery from oxidative damage
Description	Cancer therapy resistance, whether pre-existing or arising upon acquisition of de novo mutations and via non-genetic adaptation, is still a clinical challenge. Multiple anticancer drugs are thought to cause cell death via increasing mitochondrial ROS which are a bioproduct of oxidative phosphorylation. However, when properly titrated, ROS can also promote cancer cell adaptation. In keeping with this, upregulation of mitochondrial respiration coupled with high ROS-scavenging capacity is a characteristic shared by drug-tolerant cells in several cancers. Translational fidelity in the mitochondria and in the cytosol is essential for cell fitness and thus oxidative damage to the ribosomes should be prevented at all costs. While mechanisms for recognizing and repairing such damage exist in the cytoplasm, the status within mitochondria remains unclear. By performing Ascorbate PEroXidase (APEX)-proximity ligation assay directed to the mitochondrial matrix followed by isolation and sequencing of RNA associated to mitochondrial proteins, we identified the nuclear-encoded lncRNA ROSALIND as an interacting partner of ribosomes. ROSALIND is upregulated in recurrent tumours and its expression can discriminate between responders and non-responders to immune checkpoint blockade in a melanoma cohort of patients. Featuring an unusually high G content, ROSALIND serves as a substrate for oxidation. Consequently, inhibiting ROSALIND leads to an increase in ROS and protein oxidation, resulting in severe mitochondrial respiration defects. This, in turn, impairs melanoma cell viability and increases immunogenicity both in vitro and ex vivo in preclinical humanized cancer models. These findings underscore the role of ROSALIND as a novel ROS buffering system, safeguarding mitochondrial translation from oxidative stress, and shed light on potential therapeutic strategies for overcoming cancer therapy resistance.
HostingRepository	PRIDE
AnnounceDate	2024-09-20
AnnouncementXML	Submission_2024-09-20_02:39:26.630.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD047963
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vasiliki Katopodi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-19 12:35:42	ID requested
⏵ 1	2024-09-20 02:39:27	announced

10.1038/s41418-024-01377-4;

10.6019/PXD047963;

Katopodi V, Marino A, Pateraki N, Verheyden Y, Cinque S, Jimenez EL, Adnane S, Demesmaeker E, Scomparin A, Derua R, Groaz E, Leucci E, The long non-coding RNA ROSALIND protects the mitochondrial translational machinery from oxidative damage. Cell Death Differ, ():(2024) [pubmed]

submitter keyword: Human, melanoma, PDX, targeted therapy, RNA pull-down, RAP-MS

Eleonora Leucci
contact affiliation	Laboratory for RNA Cancer Biology (LRCB), Department of Oncology, KU Leuven, Belgium
contact email	eleonora.leucci@kuleuven.be
lab head
Vasiliki Katopodi
contact affiliation	KU Leuven
contact email	vasiliki.katopodi@kuleuven.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047963
     1. Label: PRIDE project
     2. Name: ROSALIND protects the mitochondrial translational machinery from oxidative damage