TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.

TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1.

The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase+ cells and telomeric recombination in ALT+ cells.

Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved THO complex (THOC) was previously identified at human telomeres.

TFIIH moonlighting at telomeres.

Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the bulk of telomeric DNA poses severe hurdles for the semiconservative DNA replication machinery, requiring the assistance of an increasing number of specialized factors that prevent accidental telomere loss or damage events.

Detection of TERRA R-Loops at Human Telomeres.

R-loops are three-stranded nucleic acid structures composed of a DNA-RNA hybrid and a displaced DNA strand. The long noncoding RNA TERRA forms R-loops at telomeres influencing the telomeric chromatin composition and impacting on telomere maintenance mechanisms by semiconservative DNA replication, homology directed DNA repair and telomerase. Here, we describe a method to detect R-loops at telomeres, which involves immunoprecipitation with the R-loop recognizing S9.

The human telomeric proteome during telomere replication.

Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats.