GSE112379 Ribosome Quality Control complex is a proteotoxic stress sensor responsible for transcriptional downregulation

Contributors : Fernando Aprile Garcia ; Parul Tomar ; Barbara Hummel ; Ritwick SawarkarSeries Type : Other ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensProteotoxic stress activates HSF-dependent heat-shock response to transcriptionally upregulate chaperones. Stress also leads to downregulation of house-keeping genes but the cellular pathway linking stress with transcriptional downregulation is not known. Here we report that enhanced recruitment of negative elongation factors (NELF) to chromatin causes gene downregulation in human cells. Stress-induced increase in cytosolic protein ubiquitination of nascently translating proteins is required for NELF recruitment to chromatin. We identify the Ribosome Quality Control-associated Listerin 1 (Ltn1) ligase responsible for nascent protein ubiquitination during stress. Depletion of Ltn1 blocks stress-dependent NELF recruitment to chromatin and transcriptional downregulation. Consequently, metabolic changes associated with stress are attenuated in cells lacking NELF or Ltn1. Thus our work identifies a novel HSF-independent pathway that senses proteotoxic stress by nascent protein ubiquitination and affects transcriptional elongation.

Source: GEO: Gene Expression Omnibus - February 7, 2019 Category: Genetics & Stem Cells Tags: Other Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research