This proposal seeks to establish the new scientific paradigm that RNA molecules can function as hormones, traveling via the bloodstream to target organs where they are taken up and influence the activity of specific recipient cells. The conventional paradigm of the endocrine system does not include RNA molecules as a class of hormones. The motivation for trying to establish this paradigm comes from a series of facts: (i) RNA molecules have been shown to function as hormones in plants, (ii) in some animal species (e.g., worms and flies) RNA has been shown to spread throughout the organism and carry information from one site to another, and (iii) we and others have found that at least one class of RNAs, known as microRNAs, are abundantly present in the blood of healthy humans and specific microRNAs accumulate in disease states such as cancer. To establish this new paradigm, we will focus on microRNAs secreted into the blood by cancer cells and use mouse models to determine whether the microRNAs are taken up by and influence distant organs and tissues. In addition, we will purify microRNAs in their natural state from blood and determine whether if re-injected into the bloodstream they can travel to specific target sites and have a hormone-like action. Establishing this new paradigm would have a major impact not only on basic understanding of human physiology but could also open up new ways of diagnosing and treating disease based on RNA hormones in the blood.

Public Health Relevance

This proposal is highly relevant to human health because it seeks to identify a new type of hormone molecule that we hypothesize carries signals throughout the human body. Establishing that RNA molecules in the blood can act as hormones could lead to better methods of diagnosing and treating a variety of human diseases.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Silva, Corinne M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
Kullolli, Majlinda; Knouf, Emily; Arampatzidou, Maria et al. (2014) Intact microRNA analysis using high resolution mass spectrometry. J Am Soc Mass Spectrom 25:80-7
Arroyo, Jason D; Gallichotte, Emily N; Tewari, Muneesh (2014) Systematic design and functional analysis of artificial microRNAs. Nucleic Acids Res 42:6064-77
Nair, Viswam S; Pritchard, Colin C; Tewari, Muneesh et al. (2014) Design and Analysis for Studying microRNAs in Human Disease: A Primer on -Omic Technologies. Am J Epidemiol 180:140-52
Chevillet, John R; Kang, Qing; Ruf, Ingrid K et al. (2014) Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A 111:14888-93
Vojtech, Lucia; Woo, Sangsoon; Hughes, Sean et al. (2014) Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res 42:7290-304
Cheng, Heather H; Yi, Hye Son; Kim, Yeonju et al. (2013) Plasma processing conditions substantially influence circulating microRNA biomarker levels. PLoS One 8:e64795
Hindson, Christopher M; Chevillet, John R; Briggs, Hilary A et al. (2013) Absolute quantification by droplet digital PCR versus analog real-time PCR. Nat Methods 10:1003-5
Knouf, Emily C; Wyman, Stacia K; Tewari, Muneesh (2013) The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance. PLoS One 8:e69630
Cheng, Heather H; Mitchell, Patrick S; Kroh, Evan M et al. (2013) Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One 8:e69239
Pritchard, Colin C; Cheng, Heather H; Tewari, Muneesh (2012) MicroRNA profiling: approaches and considerations. Nat Rev Genet 13:358-69

Showing the most recent 10 out of 12 publications