Accumulating evidence indicates that some of the many RNAs identified in body fluids and cell culture medium may be functional. Although proof-of-principle and validation projects have demonstrated cell-to-cell RNA transfer, not a single mammalian extracellular RNA has been demonstrated to enter and function in a target cell, at least in a biologically relevant and robust manner. Moreover exRNA uptake has yet to be characterized in a primary mammalian model. We do not know the functional consequences for exRNA uptake, or for that matter, the consequences of uptake deficiency. Studies over the last few years have illustrated a large and diverse population of exRNAs, including microRNA and long non-coding RNA (IncRNAs) - but we have no reference set for specific tissues, nor do we have an understanding of which exRNAs are functionally important for those tissues. Likewise, we do not have any idea of the genes involved, save for two homologs for the C. elegans SID-1 exRNA transporter that are still awaiting full characterization. Whether all or only a few cell typs can uptake exRNA also remains a complete mystery. This U19 Cooperative Agreement directly addresses critical gaps in our knowledge of the fundamental principles of exRNA biogenesis, distribution, uptake, and function.

Public Health Relevance

A critical goal for medicine is to understand how the body works, and how individual cells and tissues communicate with each other. This study aims to identify and understand the functions of novel classes of extracellular RNAs, tracking their distributions in whole organisms.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19CA179513-01
Application #
8582079
Study Section
Special Emphasis Panel (ZRG1-OBT-S (50))
Program Officer
Howcroft, Thomas K
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$1,483,202
Indirect Cost
$293,979
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143