Transcriptomics

Dataset Information

295

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


ABSTRACT: 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 domain–containing 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. mRNA sequencing of induced pluripotent stem cells and 293 cell line.

ORGANISM(S): Homo sapiens  

SUBMITTER: Suneet Agarwal   Patrick Cahan  Boris Boyraz 

PROVIDER: E-GEOD-81507 | ArrayExpress | 2016-08-02

SECONDARY ACCESSION(S): SRP075264GSE81507PRJNA321841

REPOSITORIES: GEO, ArrayExpress, ENA

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