RNA is one of the most primitive molecules associated with life that has awakened most interest over the last decade; a sister molecule to cellular DNA from which it originates via a process called transcription. Seven years ago a team from the Spanish National Cancer Research Centre (CNIO) discovered that the DNA regions that contained telomeres, despite their compact and hard-to-access structure, generated RNAs that they christened TelRNAs or TERRA.

Now, the same team has discovered that TERRAs do not originate in all telomeres that protect the 20 murine chromosomes, but do exclusively in chromosome 18 and, to a lesser extent, in chromosome 9. This peculiarity sets the stage for future genetic manipulation in mice with the aim of researching the in vivo role of these molecules in telomere biology and in illness.

Telomeres are DNA structures that are found at the ends of chromosomes to protect them and ensure cell viability. They play a key role in ageing and in ageing-associated illnesses such as cancer, or cardiovascular disease.  To date, very little is known about the RNAs produced from telomeres.  Researchers knew that once they are synthesised they associate with telomeres, but didn’t know the complete sequence or where they originate from in the genome.

Using massive sequencing data analysis the team has concluded that murine TERRAs originate from the telomeres of chromosome 18 and, to a lesser extent, from chromosome 9.

Once TERRA were transcribed the group found that they associated with the telomeres that protect the 20 murine chromosomes [not simultaneously], and not just with their telomere of origin. The researcher emphasises that this union is important for the ultimate protection of chromosomes because when TERRA levels fall using molecular tools, damage is caused in the telomere.

The discovery of the genomic origin of TERRA will allow the medical community to design molecular and genetic tools in order to study their functional role in the normal development of the mouse, as well as their role in illnesses.

The team are already generating new mouse strains that contain modifications in the regions TERRAs originate from, which will set the stage for understanding the role of these molecules and advance the frontier of knowledge regarding telomeres.

Source:  Centro Nacional de Investigaciones Oncologicas (CNIO)