Transcriptomic analysis of CAFs with silencing of TERRA lnRNA

Here, we identify a telomere-derived RNA–protein signaling axis that links genome integrity and fibroblast plasticity. We show that the long non-coding RNA TERRA, transcribed from telomeres, is upregulated in CAFs across multiple human skin cancers following loss of androgen receptor (AR) expression.

Elevated TERRA enhances telomeric DNA damage and activates a CAF-specific transcriptional program. Through proteomic profiling, we identify the RNA-binding protein NONO as a critical TERRA effector. TERRA and NONO form nuclear complexes selectively in CAFs, while in normal fibroblasts NONO associates with AR.