RNA tailing machinery drives amyloidogenic phase transition

• 成果类型: Article
• 署名作者: Bokros, Michael; Balukoff, Nathan C.; Grunfeld, Alex; Sebastiao, Mathew; Beurel, Eleonore; Bourgault, Steve; Lee, Stephen
• 署名单位: University of Miami; University of Miami; University of Quebec; University of Quebec Montreal; University of Miami
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11368
• DOI: 10.1073/pnas.2316734121
• 发表日期: 2024-05-28
• 关键词: functional amyloids; poly(a) polymerase; ribosomal-rna; polyadenylation; proteins; adaptation; SEPARATION; binding; exosome; stress

摘要

The RNA tailing machinery adds nucleotides to the 3 '- end of RNA molecules that are implicated in various biochemical functions, including protein synthesis and RNA stability. Here, we report a role for the RNA tailing machinery as enzymatic modifiers intracellular amyloidogenesis. A targeted RNA interference screen identified Terminal Nucleotidyl - transferase 4b (TENT4b/Papd5) as an essential participant in the amyloidogenic phase transition of nucleoli into solid - like Amyloid bodies. Full - length - and - mRNA sequencing uncovered starRNA, a class of unusually long untemplated RNA molecules synthesized by TENT4b. StarRNA consists of short rRNA fragments linked to long, linear mixed tails that operate as polyanionic stimulators of amyloidogenesis in cells and in vitro. Ribosomal intergenic spacer noncoding RNA (rIGSRNA) recruit TENT4b intranucleolar foci to coordinate starRNA synthesis driving their amyloidogenic phase transition. The exoribonuclease RNA Exosome degrades starRNA and functions as general suppressor of cellular amyloidogenesis. We propose that amyloidogenic phase transition is under tight enzymatic control by the RNA tailing and exosome axis.