Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita.

ABSTRACT: Dyskeratosis congenita (DC) and related syndromes are inherited, life-threatening bone marrow (BM) failure disorders, and approximately 40% of cases are currently uncharacterized at the genetic level. Here, using whole exome sequencing (WES), we have identified biallelic mutations in the gene encoding poly(A)-specific ribonuclease (PARN) in 3 families with individuals exhibiting severe DC. PARN is an extensively characterized exonuclease with deadenylation activity that controls mRNA stability in part and therefore regulates expression of a large number of genes. The DC-associated mutations identified affect key domains within the protein, and evaluation of patient cells revealed reduced deadenylation activity. This deadenylation deficiency caused an early DNA damage response in terms of n

SUBMITTER: Tummala H 

PROVIDER: S-EPMC4463202 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature