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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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The long non-coding RNA ROSALIND protects the mitochondrial translational machinery from oxidative damage.

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Researchers discovered ROSALIND, a novel lncRNA that protects mitochondrial ribosomes from oxidative stress in cancer cells. This finding offers new therapeutic targets for overcoming drug resistance and improving cancer treatment outcomes.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Drug-tolerant cancer cells exhibit increased mitochondrial respiration and ROS-scavenging.
  • Protecting mitochondrial ribosomes from oxidative damage is crucial for cell survival, but mechanisms are unclear.
  • Oxidative stress impacts translational fidelity, essential for cellular fitness.

Purpose of the Study:

  • To identify mechanisms protecting mitochondrial ribosomes from oxidative damage.
  • To investigate the role of nuclear-encoded lncRNAs in mitochondrial protection.
  • To explore ROSALIND as a potential therapeutic target in cancer.

Main Methods:

  • Ascorbate Peroxidase (APEX)-proximity ligation assay in the mitochondrial matrix.
  • Isolation and sequencing of RNA associated with mitochondrial proteins.
  • Analysis of ROSALIND expression in patient tumor samples and its functional impact.

Main Results:

  • Identified ROSALIND, a nuclear-encoded lncRNA interacting with mitochondrial ribosomes.
  • ROSALIND is upregulated in recurrent tumors and predicts response to immune checkpoint blockade.
  • Inhibiting ROSALIND increases ROS, impairs mitochondrial respiration, and reduces melanoma cell viability.
  • ROSALIND acts as a ROS buffering system, protecting mitochondrial translation.

Conclusions:

  • ROSALIND is a novel ROS-scavenging lncRNA safeguarding mitochondrial translation.
  • ROSALIND plays a critical role in cancer cell adaptation to oxidative stress.
  • Targeting ROSALIND may offer a strategy to overcome cancer therapy resistance and enhance immunogenicity.