Transcriptome analysis of human patients with telomere biology disorders having mutations in PARN gene

• Poly(A)-specific ribonuclease (PARN) is a eukaryotic deadenylating enzyme that removes poly(A) tails of RNAs, including mRNAs and ncRNAs. Mutations in human PARN are associated with developmental delay and telomere biology disorders. We have previously described a group of human patients with mutations in PARN that presented heterogeneity in disease phenotypes. Here, we have characterized the transcriptome of these patients by investigating the differential gene expression to identify metabolic pathways that were affected in these patients. Patients with lesions in PARN were all affected in the same metabolic pathways: ribosome/translation, cell-cell adhesion and cell signaling pathways. This suggests that these pathways could be crucial for the development of a severe disease state and influence penetrance of the disease. We also identified major defects in snoRNAs, scaRNAs and miRNAs profiles. Interestingly a miRNA cluster miR-let7c/miR99a/miR-125b was affected in one patient. This miRNA cluster has anti-tumorigenic properties, suggesting that deficiency of PARN could result in the development of cancer. Overall, this study has identified metabolic pathways that are affected in PARN deficient patients. The identified pathways could play a role in development of TBDs.

Subject headings

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

PARN

snoRNAs

scaRNAs

miRNAs

telomere biology disorders

Medicinsk genetik

Medical Genetics

Biology with specialization in Molecular Biology

Biologi med inriktning mot molekylärbiologi

Publication and Content Type

vet (subject category)

ovr (subject category)