Analysis of the role of CARM1 in telomere maintenance

Abstract

<p>Recent data suggest that protein arginine methyltransferase 1 (PRMT1) plays a role in telomere length maintenance and telomere stability. PRMT1 has been shown to methylate the basic domain of TRF2 and depletion of PRMT1 leads to the formation of telomere doublets in primary cells and telomere shortening in cancer cells. Additionally mass spectrometry data suggest candidate arginine residues in TRF1 and TRF2 that are mono- or di-methylated. These data suggest that arginine methylation and thus PRMT enzymes may playa role in telomere biology.</p> <p>Because PRMT1 has been shown to play a role in telomere maintenance, we decided to look for a role of another PRMT enzyme, coactivator associated arginine methyltransferase 1 (CARM1), on telomere biology. To determine if CARM1 plays a role in telomere length maintenance, hTERT-BJ cells were depleted for CARM1. Initially, a senescent phenotype was observed; however, this phenotype was not reproducible. Subsequently, I have shown that these cells do not accumulate telomere or genomic instability or a change in growth. To determine if CARM1 plays a role in telomere length maintenance, hTERT-BJ, HeLaII, and MCF-7 cells were depleted of CARM1 and cultured long term. Southern blot analysis indicated no change in telomere length dynamics over time upon depletion of CARM1 compared to control cells. Thus these results suggest that CARM1 does not playa role in telomere length maintenance.</p> <p>The laboratory of Linger identified telomeres to be transcribed into telomere repeat-containing RNA termed TERRA. The mechanism of TERRA regulation is still to be elucidated. Because CARM1 is a transcriptional coactivator, we hypothesized that CARM1 play a role in TERRA transcription. Northern blot analysis conducted in hTERT-BJ and MCF-7 cells depleted of CARM1 revealed no role for CARM1 in TERRA regulation.</p>