BARCELONA — Sonia V. Forcales and Gabrijela Dumbovic led a study characterizing the SST1/NBL2 macrosatellites and identifying a non-coding RNA called TNBL. The study was published in the journal Trends in Genetics.

The researchers identified the SST1/NBL2 macrosatellites as large tandemly repeated primate-specific DNA sequences. These sequences are primarily located on acrocentric chromosomes and exhibit high structural complexity and dynamic epigenetic regulation. The SST1/NBL2 regions produce non-coding RNAs, and in tumor cells, these regions frequently undergo demethylation.

A focus of the study was the characterization of TNBL, a non-coding RNA derived from NBL2 regions that is frequently hypomethylated in tumors. TNBL interacts with molecular factors involved in RNA splicing, the DNA damage response, and nucleolar function. Genomic regions containing SST1/NBL2 have also been linked to Robertsonian translocations, which are the most common chromosomal rearrangements in humans. Robertsonian translocations involving chromosome 21 can cause a form of trisomy 21.

Historically, repetitive genomic regions were difficult to study due to technological limitations in sequencing resolution. Previous conventional genome assemblies frequently excluded, fragmented, or poorly represented SST1/NBL2 regions. However, long-read sequencing technologies and telomere-to-telomere genome assemblies have improved the reconstruction of these repetitive genomic regions. Altered methylation of repetitive genomic regions, including SST1/NBL2 and the D4Z4 macrosatellite, has been documented in ICF syndrome, a condition characterized by immunodeficiency, chromosomal instability, and facial anomalies.

Forcales, the Principal Investigator, said, "This suggests possible connections between the repetitive genome and functional molecular processes in tumour biology. However, we still do not know to what extent SST1/NBL2 are directly involved in these processes or what the exact underlying mechanism is." She said, "We are still in a basic research phase, but if we confirm that these RNAs functionally contribute to tumour processes, it could open up new avenues to explore their role as biomarkers or therapeutic vulnerabilities."

No independent assessment was available for this report.