RT Journal Article
SR Electronic
T1 Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch Syndrome fibroblasts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.29.925131
DO 10.1101/2020.01.29.925131
A1 Cindy Tatiana Báez-Becerra
A1 Estefania Valencia-Rincón
A1 Karen Velásquez-Méndez
A1 Nelson J. Ramírez-Suárez
A1 Claudia Guevara
A1 Adrian Sandoval-Hernandez
A1 Carlos E. Arboleda-Bustos
A1 Leonora Olivos-Cisneros
A1 Gabriela Gutiérrez-Ospina
A1 Humberto Arboleda
A1 Gonzalo Arboleda
YR 2020
UL http://biorxiv.org/content/early/2020/01/30/2020.01.29.925131.abstract
AB Recently, mutations in the RNA polymerase III subunit 3A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A have important roles in the regulation of transcription of small RNAs, including tRNA, 5S rRNA and U6 snRNA. We aim to describe cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control were grown. Mutation in POLR3A causes a decreased in the expression of POLR3A mRNA and protein and a sharp increased of mutant protein. In addition, there was an increased in its nuclear localization. These changes were associated to an increase number and area of nucleoli, a significantly larger nuclear area, and a high increased in the expression of pP53 and pH2AX. All these changes were associated to premature senescence. The present observations add to our understanding of the differences between HGPS and WRS, and opens new alternatives to study cell senesce and human aging.