Telomeric Repeat-Containing RNA (TERRA) and Telomerase Are Components of Telomeres During Mammalian Gametogenesis1

Abstract

Telomeres are ribonucleoprotein structures at the end of chromosomes composed of telomeric DNA, specific-binding proteins, and noncoding RNA (TERRA). Despite their importance in preventing chromosome instability, little is known about the cross talk between these three elements during the formation of the germ line. Here, we provide evidence that both TERRA and the telomerase enzymatic subunit (TERT) are components of telomeres in mammalian germ cells. We found that TERRA colocalizes with telomeres during mammalian meiosis and that its expression progressively increases during spermatogenesis until the beginning of spermiogenesis. While both TERRA levels and distribution would be regulated in a gender-specific manner, telomere-TERT colocalization appears to be regulated based on species-specific characteristics of the telomeric structure. Moreover, we found that TERT localization at telomeres is maintained throughout spermatogenesis as a structural component without affecting telomere elongation. Our results represent the first evidence of colocalization between telomerase and telomeres during mammalian gametogenesis.

Transcription of highly repetitive tandemly organized DNA in amphibians and birds: A historical overview and modern concepts

“…This fact supports the idea that telomeric transcripts might participate in telomere stability during gametogenesis that allows cells to divide properly and to form balanced gametes. 84,85 It should be noted that it is quite difficult to obtain mammalian female gametes preparations, especially preparations of oocytes at the first meiotic division, which limited the studies of the biological role of TERRA RNA and TERT in gametogenesis. Transcription of telomere repeat that was demonstrated at the termini of lampbrush chromosomes 40,44,45 makes amphibian and avian oocytes an attractive model for elucidation of TERRA RNA functions and biogenesis.…”

A single-cell assay for telomere DNA content shows increasing telomere length heterogeneity, as well as increasing mean telomere length in human spermatozoa with advancing age

“…Mice engineered to have short telomeres also display abnormal early embryo development [2]. Also, the importance of telomere homeostasis in fertility was recently demonstrated in mammalian germ cells [12,13], where authors showed that telomere structure and homeostasis is compromised in spermatocytes from patients with idiopathic infertility [13].…”

On the origin of Robertsonian fusions in nature: evidence of telomere shortening in wild house mice

“…Table summarizes all data (telomeres scored, mean and SE (TFUs), percentage of short arms and percentage of metacentric chromosomes) per specimen and type of chromosomal arm. We found that mouse cells showed wider telomere length ranges and higher mean telomeric lengths than human (HeLa) cells confirming previous observations (Zijlmans et al ., ; Reig‐Viader et al ., ).…”

“…At least 28 metaphases were analysed per cell line (Table 1) given that this sample size gives comparable results to conventional southern analysis (Poon et al, 1999;Vera & Blasco, 2012). Telomere lengths were obtained in terms of arbitrary telomere fluorescence units (TFUs) following previous studies (Reig-Viader et al, 2014).…”

“…Several factors have been invoked for the appearance of Rb fusions in mammalian species; these include chromosome size, GC and DNA content, gene density, illegitimate recombination between repetitive sequences and telomere loss or inactivation (Slijepcevic, 1998;Garagna et al, 2001;Ruiz-Herrera et al, 2010;Wesche & Robinson, 2012). Telomeres are ribonucleoprotein structures composed of TTAGGG tandem repeats, a protein complex (shelterin) and noncoding telomeric RNA (TERRA) that cap the ends of eukaryotic chromosomes to protect them from being recognized as double-strand breaks (DSBs) (Azzalin et al, 2007;O'Sullivan & Karlseder, 2010;Reig-Viader et al, 2014). Therefore, Rb fusions would require either the elimination or the inactivation of telomeres prior to the chromosomal rearrangement.…”