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. 2015 Apr 14;6:143. doi: 10.3389/fgene.2015.00143

Figure 1.

Figure 1

Proposed functions of TERRA at functional and dysfunctional telomeres. (A) TERRA expression promotes heterochromatin formation at telomeres. TERRA interacts with several proteins at telomeres including TRF2, H3K9me3, origin replication complex 1 (ORC1), HP1, and MORF4L2 proteins. TERRA molecules act as scaffold recruiting chromatin remodeling factors to chromosome ends. (B) Expression of TERRA is required for proper capping of telomeres. hnRNPA1 displaces RPA from telomeric single-stranded overhangs. TERRA transcripts interact with hnRNPA1. TERRA-hnRNPA1 interaction removes hnRNPA1 from chromosome ends allowing POT1 to bind the telomeric single-stranded overhangs. (C) TERRA participates to DNA damage response triggered by dysfunctional telomeres. Depletion of TRF2 results in dysfunctional telomeres and increased TERRA expression. TERRA interacts with lysine-specific demethylase 1 (LSD1). Elevated TERRA levels in TRF2-depleted cells promote nucleolytic processing of uncapped telomeres by favoring the recruitment of a LSD1-MRE11 complex at telomeres (1). TERRA molecules interact with SUV39H1 histone methyltransferase. TERRA-SUV39H1 interaction promotes H3K9 methylation (H3K9me3) at dysfunctional telomeres and chromosome end-to-end fusions (2).