- What is meant by "extracellular RNA"?
- Why do scientists want to study exRNAs?
- What diseases have been linked to changes in exRNAs?
- What is the goal of the NIH Common Fund program on Extracellular RNA Communication?
- What research is being supported by the Extracellular RNA Communication program?
- If I’m not part of the ERC Program Consortium, can I still access the data?
1. What is meant by "extracellular RNA"?
Most RNA works inside cells to translate genes into proteins that are necessary for living organisms to function. Other types of RNA control which proteins and the amount of those proteins the cells make. Until recently, scientists believed RNA worked mostly inside the cell that produced it. Now, recent findings show cells can release RNA in the form of extracellular RNA (exRNA), to travel through body fluids and affect other cells. ExRNA can act as a signaling molecule, communicating with other cells and carrying information from cell to cell throughout the body. The cells that produce exRNAs can be endogenous (part of the body) or from exogenous sources, including microbes living in our bodies or from food products, such as plants that we eat. ExRNAs include microRNA, mRNA, and long non-coding RNA which are secreted and found in all body fluids examined, including blood, saliva, urine, breast milk, cerebral spinal fluid (CSF), amniotic fluid, ascites, and pleural effusions. When in circulation, exRNAs may be encapsulated in extracellular vesicles (EVs) or associated with lipids or proteins.
2. Why do scientists want to study exRNAs?
Very little is currently known about exRNAs and the roles they play in human health and disease. Do cells send “messages” to distant cells using exRNA? Do diseased cells release specific exRNAs that could cause healthy cells to become diseased? Do exRNAs from the foods that we eat or the microbes on our bodies affect our own cells? Could some exRNAs make us more susceptible to disease, or conversely, could some exRNAs protect us from disease? There is a tremendous opportunity to learn more about this entirely new paradigm of intercellular and inter-species information exchange to catalyze research in this nascent field. Researchers hope to use some kinds of exRNA as biomarkers, or indicators of the presence, absence, or stage of a disease. These biomarkers may enable scientists to understand and diagnose diseases earlier and more effectively. Scientists may also be able to harness the power of exRNAs to develop novel molecular treatments for diseases.
3. What diseases have been linked to changes in exRNAs?
Although the study of exRNA is still in the very early stages, current research is exploring the association between various diseases and changes in exRNAs. These diseases include several types of cancer, neurological disorders, heart disease, kidney disease, and more. It is currently unknown what impact disease-specific exRNAs may have on other cells in the body. Additionally, exRNAs derived from exogenous sources, such as microbes or food, may affect health and disease risk. More research is needed before scientists will be able to understand the relationship between exRNAs and disease.
4. What is the goal of the NIH Common Fund program on Extracellular RNA Communication?
The Common Fund Extracellular RNA Communication (ERC) Program (http://commonfund.nih.gov/exrna/) has been developed to address critical issues in exRNA research. Both fundamental scientific discovery and innovative tools and technologies will be required to advance the field. The ERC program consists of five integrated initiatives:
- ExRNA biogenesis, distribution, uptake, and function (RFA-RM-12-012): To discover basic fundamental principles about how cells make and release exRNA (biogenesis), how and where exRNA travels through body fluids to other cells (distribution), how cells take in exRNA that is traveling through body fluids (uptake), and how exRNA changes the function of cells (function). This initiative is also supporting the development of molecular tools, technologies, and imaging modalities to enable these studies
- Reference profiles of human exRNAs (Funding Opportunity Announcement anticipated late summer/early fall 2013): To generate a reference catalog of exRNAs present in the body fluids of normal healthy individuals that would facilitate disease diagnosis and therapeutic outcomes
- Clinical utility of exRNAs for biomarker development (RFA-RM-12-013): To develop reliable, well-defined and clinically relevant biomarkers derived from extracellular RNA that measure tangible benefits for patients in terms of how they feel, function, and survive in clinical trials
- Clinical utility of exRNAs for therapy development (RFA-RM-12-014): To develop and demonstrate the potential for clinical utility of exRNAs as therapeutic agents, and to develop tools and technologies to enable engineered RNAs to be packaged into extracellular vesicles or associated with RNA-binding proteins for use as extracellular delivery vehicles
- Data management and resource repository for exRNA (RFA-RM-12-010): To integrate the efforts of all of the funded components of the ERC program and serve as a community-wide resource for ExRNA standards, protocols, and data.
5. What research is being supported by the Extracellular RNA Communication program?
Awards for four initiatives are expected to be announced in August, 2013. Once announced, information on all awards can be found on the Extracellular RNA Communication program website (http://commonfund.nih.gov/exrna/), under the “Research Funding” menu at the top of the page.
6. If I’m not part of the ERC Program Consortium, can I still access the data?
Yes, you can! One of the goals of the ERC Program is to generate a community wide exRNA Atlas and database of tools and technologies. Once developed, the exRNA Atlas can be accessed through the Extracellular RNA Communication website (http://commonfund.nih.gov/exrna/). The exRNA Atlas will be accessible to the broader scientific community with tools to facilitate data mining by both novice and experienced researchers. Data generated from this program also will be deposited into NCBI’s dbGaP (http://www.ncbi.nlm.nih.gov/gap).