# Role of ER-membrane contacts in biogenesis of RNA-containing EVs

> **NIH NIH P01** · VANDERBILT UNIVERSITY · 2021 · $351,002

## Abstract

Project 1 Summary:
Extracellular vesicles (EVs) carry a variety of RNAs, including both coding and noncoding RNAs. These
RNAs have the potential to influence cell and tissue phenotypes. Indeed for miRNAs there are now many
examples of EV-carried miRNA controlling gene expression and function in recipient cells. RNA-Seq analyses
have demonstrated specific enrichment of some RNAs in EVs, compared to the cellular content. However, very
little is known about the specific mechanisms by which RNA is transported into EVs.
 The current paradigm, based on several studies, is that RNA-binding proteins (RBPs) are responsible
for the selective and specific inclusion of RNAs in EVs. However, how those RBPs connect to cellular
membranes to be incorporated into shed microvesicles (MVs) or late endosome-derived exosomes is
unknown. A notable finding is that many RBPs identified in EVs are typically associated with the endoplasmic
reticulum (ER) in cells, suggesting a potential role for the ER in transfer of those moieties to other organelles.
Furthermore, the RNA-induced silencing complex is assembled on mRNA-ribosome complexes associated
with the ER (rough ER), suggesting a route for miRNA-RBP association with the ER and subsequently other
membranes. Based on these findings and our preliminary data, we hypothesize that ER-plasma membrane
(PM) and ER-multivesicular endosome (MVE) membrane contact sites (MCS) are critical for transfer of RNAs
and RBPs into shed microvesicles and exosomes. We further hypothesize that signaling and lipid transfer
events taking place at these contacts further regulate RNA transport into vesicles. We will test these
hypotheses and determine the impact of MCS on transfer of RNAs to recipient cells and CRC tumor growth
and cetuximab resistance.

## Key facts

- **NIH application ID:** 10087488
- **Project number:** 5P01CA229123-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Alissa M Weaver
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,002
- **Award type:** 5
- **Project period:** 2020-01-22 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087488

## Citation

> US National Institutes of Health, RePORTER application 10087488, Role of ER-membrane contacts in biogenesis of RNA-containing EVs (5P01CA229123-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10087488. Licensed CC0.

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