# Endosome transcriptomics reveal trafficking of Cajal bodies into multivesicular bodies

## TL;DR

This study reveals that nuclear RNA complexes are trafficked into endosomes, providing a new mechanism for their degradation and recycling.

## Contribution

The study identifies for the first time that nuclear RNAs are transported to multivesicular bodies via endosomal sorting complexes.

## Key findings

- Nuclear RNA–protein complexes traffic into endosomes, a previously unknown phenomenon.
- RNA trafficking to MVBs requires endosomal sorting complexes and phospholipids.
- Blocking VPS34 prevents turnover of nuclear RNAs in MVBs.

## Abstract

Endosomes are cytoplasmic membrane-bound subcellular organelles that are sites for exosome biogenesis, a class of extracellular vesicles, which may participate in intercellular communication and maintaining cellular homeostasis by their secretion of selected proteins and small-RNAs. Previous studies have focused solely on the transcriptome of exosomes; however, very little is known about the identity of RNAs inside the endosomes and mechanisms that govern their localization. Here, we report a comprehensive endosome transcriptome and provide evidence that several nuclear RNA–protein complexes sort into endosomes, a previously unappreciated phenomenon. We show that this process requires activity of endosomal sorting complexes and phospholipids characteristic of cellular endocytic compartments. Our study provides a mechanism for recycling of nuclear ribonucleoproteins (RNPs) by cytoplasmic endocytic pathway.

All eukaryotic cells secrete exosomes, a type of extracellular vesicles derived from the endocytic compartments known as multivesicular bodies (MVBs), or late endosomes (LEs). Exosomes contain a diverse range of cargo such as nucleic acids, proteins, lipids, and small molecules but whether these contents have a biological function remains an area of intense investigation. Over the last decade, numerous studies have described the transcriptome of exosomes but very little is known about the RNA content of the MVBs, the source compartment for exosome biogenesis. Here, we determine the small-RNA transcriptome of highly purified MVBs and report that various classes of nuclear small regulatory RNAs such as small-Cajal body associated RNAs, small-nucleolar RNAs, and small-nuclear RNAs traffic to MVBs. We show that this RNA-trafficking requires the function of endosomal sorting complexes required for transport (ESCRT) machinery but is independent of canonical LC3 lipidation mediated selective autophagy. Furthermore, blocking the activity of a PI3K Class 3 enzyme, VPS34, required for recruitment of the ESCRT machinery to the endosome, prevents the turnover of these nuclear RNAs in MVBs. Our results provide a mechanism for targeting nuclear ribonucleoprotein complexes, such as Cajal bodies, for degradation and turnover by the cytoplasmic endo-lysosomal pathway.