bioRxiv Science⌕ Search

Biology subjects

Iben, S.

Publications and source records attributed to Iben, S..

2 recordsLinked to original sources
bioRxiv2026

ER-stress signaling and Alzheimer's proteins adjust the quality of human protein synthesis

Proteostasis is the balance of protein synthesis, protein maintenance and protein degradation. Proteostasis is disturbed in neurodegenerative disorders like Alzheimers disease (AD) of the aging human body. Protein synthesis by the ribosome is the most error-prone process in gene expression. If and how the error-rate of protein synthesis is regulated during human aging and contributes to AD is unknown. Here we show that ribosomal error-rate is adapted in cellular models of human aging, but not in mouse aging. This adaptation involves ER-stress signaling and the Alzheimers disease-related proteins amyloid-beta precursor protein and presenilin 1. Our results suggest that ribosomal error-rate is a relevant parameter in human aging and disease.

cell biology↗
bioRxiv2020

Nucleolar TFIIE plays a role in ribosomal biogenesis and performance

Ribosome biogenesis is a highly energy-demanding process in eukaryotes which requires the concerted action of all three RNA polymerases. In RNA polymerase II transcription, the general transcription factor TFIIH is recruited by TFIIE to the initiation site of protein-coding genes. Distinct mutations in TFIIH and TFIIE give rise to the degenerative disorder trichothiodystrophy (TTD). Here we uncovered an unexpected role of TFIIE in ribosomal RNA synthesis by RNA polymerase I. With high resolution microscopy we detected TFIIE in the nucleolus where TFIIE binds to actively transcribed rDNA. Mutations in TFIIE affects gene-occupancy of RNA polymerase I, rRNA maturation, ribosomal assembly and performance. In consequence, the elevated translational error rate with imbalanced protein synthesis and turnover results in an increase in heat-sensitive proteins. Collectively, mutations in TFIIE - due to impaired ribosomal biogenesis and translational accuracy - lead to a loss of protein homeostasis (proteostasis) which can partly explain the clinical phenotype in TTD.

cell biology↗