Biology subjects

Akimoto, T.

Publications and source records attributed to Akimoto, T..

2 recordsLinked to original sources

bioRxiv2024

The Rubicon-WIPI axis regulates exosome biogenesis during aging

Cells release intraluminal vesicles (ILVs) in multivesicular bodies as exosomes to communicate with other cells. Although recent studies suggest an intimate link between exosome biogenesis and autophagy, the detailed mechanism is not fully understood. Here we employed comprehensive RNAi screening for autophagy-related factors and discovered that Rubicon, a negative regulator of autophagy, is essential for exosome release. Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Interactome analysis of WIPI2d identified the ESCRT components that are required for ILV formation. Notably, we found that Rubicon is required for an age-dependent increase of exosome release in mice. In addition, small RNA sequencing of serum exosomes revealed that Rubicon determines the fate of exosomal microRNAs associated with cellular senescence and longevity pathways. Taken together, our current results suggest that the Rubicon-WIPI axis functions as a key regulator of exosome biogenesis and is responsible for the age-dependent changes in exosome quantity and quality.

cell biology↗

bioRxiv2020

microRNAs slow translating ribosomes to prevent protein misfolding

An evolutionarily conserved mechanism, use of non-optimal codons, slows ribosomes during translation to allow proper folding of nascent polypeptides. However, until now, it was unknown whether any eukaryote-specific mechanisms exist for this purpose. Here, we propose that miRNAs slow translating ribosomes to prevent protein misfolding, with little negative effect on protein abundance. To prove this, we bioinformatically analyze ribosome profiling and miRNA binding sites and biochemically confirm that miRNA deficiency causes severe misfolding, which is rescued by slowing translating ribosomes. We demonstrate that non-cleaving shRNAs, targeting regions where elongation rates become faster in miRNA-deficient cells, improve protein folding with minimal effects on protein abundance. These results reveal broader functionality of miRNAs and a previously unknown mechanism to prevent protein misfolding. One Sentence SummaryEukaryote use of miRNAs prevents protein misfolding in a target-specific manner.

biochemistry↗