Functional characterization of the TERRA transcriptome at damaged telomeres

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Telomere deprotection, caused by telomere shortening or loss of TRF2, triggers a DNA damage response (DDR) leading to cellular senescence.
• The telomeric long noncoding RNA TERRA is involved in regulating the structure and processing of deprotected telomeres.

Purpose of the Study:

• To characterize the human TERRA transcriptome at normal and TRF2-depleted telomeres.
• To elucidate the role of TERRA in the telomeric DNA damage response.

Main Methods:

• Analysis of human TERRA transcriptome.
• TRF2 depletion experiments.
• Investigation of TERRA association with SUV39H1.

Main Results:

• TERRA is upregulated upon TRF2 depletion at all transcribed telomeres.
• TRF2 represses TERRA transcription via its homodimerization domain.
• TERRA associates with SUV39H1, promoting H3K9me3 accumulation at damaged telomeres and end-to-end fusions.

Conclusions:

• The study defines the TERRA landscape and its critical functions in the telomeric DNA damage response.
• TERRA plays a significant role in processes relevant to cancer and aging.