Telomeric Repeat-Containing RNA (TERRA): A Review of the Literature and First Assessment in Cutaneous T-Cell Lymphomas

Abstract

Telomeric Repeat-containing RNA (TERRA) are long non-coding RNAs transcribed from telomeric DNA sequences from multiple chromosome ends. Major research efforts have been made to understand TERRA roles and functions in several physiological and pathological processes. We summarize herein available data regarding TERRA's roles in human cells and we report the first investigation in cutaneous T-cells lymphomas (CTCL) using real-time PCR. Among the TERRA analysed, our data suggest a particular role for TERRA 16p downregulation and TERRA 11q upregulation in CTCL lymphomagenesis.

Keywords: TERRA; cutaneous T-cell lymphomas; non-coding RNA; sézary syndrome; telomerase; telomere.

Figure 1

Telomeric DNA, proteins and TERRA. (A) Schematic representation of a telomeric region. (B) T-loop and D-loop configurations, along with the Shelterin proteins. (C) G-quadruplex structure. (D) The shelterin complex including the following proteins Telomeric-Repeat-binding Factor 1 and 2 (TRF1 and TRF2), Protection of Telomeres 1 (POT1), TRF1-Interacting Nuclear protein 2 (TIN2), TIN2-interacting protein (TPP1), and Repressor-Activator Protein 1 (RAP1). (E) TERRA and R-loops.

Figure 2

Telomeric repeat containing RNA (TERRA) in CTCL cells. TERRA from chromosome ends 1q, 9p, 10q, 11q, 15q, 16p and XpYp were analysed in CTCL cells, including SS patients (n = 4) and CTCL cell lines representative of different CTCL subtypes: c-ALCL, T-MF, and SS), and then compared with healthy donors (n = 9). (A) The total TERRA expression was evaluated. Before the analysis of our cells of interest, the RT-qPCR protocol for quantification of TERRA was validated in HeLa and U2OS cell lines (in grey). We confirmed that U2OS and HeLa cells express different TERRA levels [56]. Data are expressed as mean ± SD. (B) For CTCL cells we presented the (1) TERRA profile for seven telomeric transcripts in a heat map: horizontal axis = TERRA transcripts; vertical axis = cells analysed. Low expression levels are displayed in light blue, and high expression levels in dark blue. (2) Statistical analysis from TERRA profiling. Significance level: p = 0.05.

Figure 3

hTERT impact on TERRA transcription. The expression of TERRA from chromosome ends 1q (A), 9p (B), 10q (C), 11q (D), 15q (E), 16p (F) and XpYp (G) were analysed in T-MF and SS cells overexpressing hTERT and in their respective controls. Statistical analysis results are displayed on each graph. Significance level: p = 0.05. Data are expressed as mean ± SD.

Figure 4

Functional impact of hTERT overexpression on telomerase activity and telomere length. Telomerase canonical functions were evaluated in SS cells overexpressing hTERT, through the assessment of (A) telomerase activity and (B) telomere length. Statistical analysis results are displayed on each graph. Significance level: p = 0.05.