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Updated: Jun 25, 2025
05:48
Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
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RNA tailing machinery drives amyloidogenic phase transition
Michael Bokros1,2, Nathan C Balukoff1,2, Alex Grunfeld1,2
1Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136.
Summary
The RNA tailing machinery, including TENT4b, modifies RNA to control cellular amyloidogenesis. This process involves starRNA synthesis and degradation by the RNA Exosome, revealing a new enzymatic axis regulating amyloid formation.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- The RNA tailing machinery adds nucleotides to RNA 3'-ends, influencing protein synthesis and stability.
- Intracellular amyloidogenesis, the formation of amyloid bodies, is a critical cellular process.
- The role of RNA modification in amyloidogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of RNA tailing machinery in intracellular amyloidogenesis.
- To identify key enzymes and RNA molecules involved in nucleolar amyloid body formation.
- To elucidate the regulatory mechanisms controlling cellular amyloidogenesis.
Main Methods:
- RNA interference screening to identify essential genes.
- Full-length and mRNA sequencing to discover novel RNA species.
- In vitro and cellular assays to study amyloidogenesis and RNA interactions.
Main Results:
- Terminal Nucleotidyl-transferase 4b (TENT4b) is essential for nucleolar amyloidogenesis.
- TENT4b synthesizes starRNA, long untemplated RNAs that stimulate amyloidogenesis.
- Ribosomal intergenic spacer noncoding RNA (rIGSRNA) recruits TENT4b to nucleoli.
- The RNA Exosome degrades starRNA and suppresses amyloidogenesis.
Conclusions:
- The RNA tailing machinery, specifically TENT4b, acts as an enzymatic modifier of intracellular amyloidogenesis.
- StarRNA molecules synthesized by TENT4b promote amyloid body formation.
- The RNA tailing and RNA Exosome axis tightly controls amyloidogenic phase transitions.
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