Using a sequencing approach called PANDORA-seq, researchers searched for previously hidden small RNAs in the liver, the organ that controls cholesterol metabolism. They identified a single molecule, tsRNA-Glu-CTC, that was highly abundant in the liver and whose levels changed with cholesterol; the team reported that it made up more than 65% of the detectable tRNA-derived small RNAs in their samples.
The study linked tsRNA-Glu-CTC to SREBP2 (Sterol Regulatory Element-Binding Protein 2), a key protein that acts as a master regulator of cholesterol production. Higher tsRNA-Glu-CTC boosted SREBP2 activity and turned on genes that synthesize cholesterol.
In mice, researchers used an antisense oligonucleotide (ASO) to lower tsRNA-Glu-CTC. Lowering the molecule reduced cholesterol and led to less severe atherosclerosis. A naturally chemically modified form of the RNA was more effective than synthetic versions, and human blood samples showed a similar association between elevated tsRNA-Glu-CTC and higher circulating cholesterol.
Difficult words
- sequence — to identify the order of genetic materialsequencing
- metabolism — chemical processes in the body that use energy
- regulator — a molecule or protein that controls activity
- synthesize — to make a chemical substance inside cells
- antisense oligonucleotide — a short strand made in a lab that blocks RNA
- modified — chemically changed to have a different form
- abundant — present in large amounts or numbers
- atherosclerosis — a disease where arteries become narrow with fat
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Discussion questions
- How could lowering a molecule like tsRNA-Glu-CTC help people with high cholesterol? Explain briefly.
- What might be advantages or concerns of using a naturally chemically modified RNA instead of a fully synthetic drug?
- What further tests or information would you want before a treatment like this is offered to people?
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