It is now clear that regulatory non-coding RNAs (ncRNAs) play important roles in the development of human cancer. While it is known that cancer-related ncRNAs vary greatly in their size and sequence, the role of their natural chemical modification in both normal and transformed cells is poorly understood. Recent studies have revealed that the small molecules CoA and NAD cap the 5'end of small RNAs in divergent bacteria. The function of these novel RNA modifications is completely unknown. I propose that small RNAs, including microRNAs and siRNAs in eukaryotes and CRISPRs in prokaryotes possess these 5'modifications. In addition, I believe that these modifications confer on RNAs an ability to covalently interact with the proteome. I will use biochemistry and genetics techniques to determine whether or not coenzyme-small RNA conjugates are present in the nematode C. elegans, how those RNAs become linked to the proteins and what novel properties such RNA-tagged proteins would show. Because cancer cells are known to have both altered metabolic states as well as aberrant expression of ncRNAs, it is possible that coenzyme-capped RNAs play a pivotal role in oncogenesis and may represent a previously undetected meeting point between small RNA biology and cellular metabolism.

Public Health Relevance

The purpose of this project is to contribute to the public's understanding of the mechanisms that cause human cancer. Many cancer-related genes are present in laboratory model organisms such as the round worm Caenorhabditis elegans. Understanding how these genes function and interact is instrumental in progressing towards our fight against cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM101802-02
Application #
8458659
Study Section
Special Emphasis Panel (ZRG1-F08-K (20))
Program Officer
Reddy, Michael K
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199