16,603 research outputs found

    Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends

    No full text
    Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat–containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity. Telomeres fulfill essential functions forchromosome stability during mitosis andmeiosis, and they equip normal human somatic cells with a cellular clock that deter-mines their replicative lifespan (1–3). Mamma-lian telomeres comprise tandem arrays of duplex 5′-TTAGGG-3 ′ repeats, with the G-rich stran

    Insertion of telomeric repeats at intrachromosomal break sites during primate evolution

    No full text
    Short blocks of telomeric-like DNA (Interstitial Telomeric Sequences, ITSs) are found far from chromosome ends. We addressed the question as to how such sequences arise by comparing the loci of 10 human ITSs with their genomic orthologs in 12 primate species. The ITSs did not derive from expansion of pre-existing TTAGGG units, as described for other microsatellites, but appeared suddenly during evolution. Nine insertion events were dated along the primate evolutionary tree, the dates ranging between 40 and 6 million years ago. Sequence comparisons suggest that in each case the block of (TTAGGG)(n) DNA arose as a result of double-strand break repair. In fact, ancestral sequences were either interrupted precisely by the tract of telomeric-like repeats or showed the typical modifications observed at double-strand break repair sites such as short deletions, addition of random sequences, or duplications. Similar conclusions were drawn from the analysis of a chimpanzee-specific ITS. We propose that telomeric sequences were inserted by the capture of a telomeric DNA fragment at the break site or by the telomerase enzyme. Our conclusions indicate that human ITSs are relics of ancient breakage rather than fragile sites themselves, as previously suggested

    CpG-island promoters drive transcription of human telomeres

    No full text
    The longstanding dogma that telomeres, the heterochromatic extremities of linear eukaryotic chromosomes, are transcriptionally silent was overturned by the discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide-rich DNA islands, shared among multiple human chromosome ends, promote transcription of TERRA molecules. TERRA promoters sustain cellular expression of reporter genes, are located immediately upstream of TERRA transcription start sites, and are bound by active RNAPII in vivo. Finally, the identified promoter CpG dinucleotides are methylated in vivo, and cytosine methylation negatively regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology

    Performance changes after two anaerobic training regimes in soccer players

    No full text
    The aim of this study was to compare the effects of two anaerobic training regimes on highintensity intermittent exercise performance evaluated by the Yo -Yo Intermittent Recovery Test level 1 (YYIR1) and 2 (YYIR2). During a 8-12-wks in-season period, nineteen sub-elite soccer players (age 24±5 years, height 177±7 cm, body mass 75±5 kg) performed either repeated sprint (RS; n=9) or speed endurance production (SEP; n=10) training twice a wk. RS training consisted of 2-4 sets of 6x5-s sprints followed by 10-15 s of passive recovery, whereas SEP training was characterized by 6-8x20-s all-out efforts interspersed with 120 s of passive recovery. After the training period, both RS and SEP group improved significantly YYIR1 (RS: 2236 vs 2480 m; SEP: 2248 vs 2580 m; p<0.001) and YYIR2 (RS: 911 vs 1078 m; SEP: 904 vs 976 m; p<0.01) performance. According to a statistical approach based on the magnitude of change, RS induced possibly greater changes in YYIR2 performance than SEP, whereas differences in YYIR1 changes were unclear. Thus, the present results show that high-intensity intermittent performance was improved after both RS and SEP training. However, in contrast to the YYIR1, where no differences were observed between the groups, in YYIR2, the RS training-induced changes seem to be possibly greater compared to SEP. A plausible explanation could be that the RS protocol induced a higher improvement in the anaerobic energy system, which is taxed to a larger extent during the YYIR2

    The politics and economics of regulatory impact assessment

    No full text
    This is the author accepted manuscript. The final version is available from the publisher via the link in this record

    Is a retrospective RPE appropriate in soccer? Response shift and recall bias

    No full text
    This study examined the acceptability of a retrospective rating of perceived exertion in soccer. Two attributes were investigated: response shift and recall bias. Response shift refers to a change in perception due to changes in internal standards and recall bias can influence the response shift assessment. Ratings were collected with the Borg-CR100 (R) scale. Study 1: during competitive season 58 players (age 22 +/- 5 years, height 178 +/- 6 cm, body mass 72 +/- 6 kg) were asked their rating following cessation of the matches and again at48 h post match. Response shift (first part of the season) was investigated by difference between the two ratings and recall bias (second part of the season) asking players whether they remembered exactly the rating given 48 h before. No response shift or recall bias were found. Study 2: 21 players (age 25 +/- 5 years, height 176 +/- 6 cm, body mass 71 +/- 7 kg) were asked ratings at the end and 48 h following a field session, equated for internal and external loads. The same session was repeated after 10 days in a randomized crossover design. No significant differences (P &gt; 0.05) between conditions were found. Retrospective rating was appropriate, however, the inconsistency of some ratings (i.e., after training) suggested it should be used only under special circumstances
    corecore