PLX056718

GSE81507: Post-transcriptional manipulation of TERC reverses molecular hallmarks of telomere disease

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The telomerase RNA component (TERC) is a critical determinant of cellular self renewal. Poly(A)-specific ribonuclease (PARN) is required for post-transcriptional maturation of TERC. PARN mutations lead to incomplete 3 end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing post-transcriptional 3 oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. Inhibition of the noncanonical poly(A) polymerase PAP-associated domaincontaining 5 (PAPD5) increased TERC levels in PARN-mutant patient cells. PAPD5 inhibition was also associated with increases in TERC stability, telomerase activity, and telomere elongation. Our results demonstrate that manipulating post-transcriptional regulatory pathways may be a potential strategy to reverse the molecular hallmarks of telomere disease. SOURCE: Patrick Cahan (patrick.cahan@jhmi.edu) - Cahan Lab Johns Hopkins University School of Medicine