The National Human Genome Research Institute (NHGRI) announced Tuesday it has funded a Weill Cornell Medicine-based Center of Excellence in Genome Sciences (CEGS) to study how RNA functions to create the patterns of protein expression seen in human tissues and disease. The multi-institution CEGS will be funded via a $12.2 million grant from the NHGRI under the leadership of Samie R. Jaffrey, the Greenberg-Starr Professor of Pharmacology at Weill Cornell Medicine. Other participating institutions include, Duke, the University of California at San Francisco, New York Institute of Technology and St. Jude Children’s Research Hospital.
The human genome encodes messenger RNA (mRNA), which carries copies of the genetic instructions that determine what proteins the cell will make and also encodes transfer RNA (tRNA) and ribosomal RNA (rRNA), which come together with mRNA in a cell to build the proteins according to their instructions.
Jaffrey’s lab is credited with developing the first screening method, about 10 years ago, that screens for the nearly 50 distinct chemical marks found on mRNA. Other researchers have since identified similar chemical marks on tRNA and rRNA and Haffrey noted that the three types of RNA appear to work together differently depending on the tissue they are in.
“We’re trying to understand how different types of RNA orchestrate patterns of protein synthesis in different types of tissues, and in disease,” Jaffrey said in a press release announcing the creation of The Center for Genomic Information Encoded by RNA Nucleotide Modifications.
One of the CEGS’s early projects will be led by Jaffrey to map the functional modifications that occur across the “transcriptome,” the complete set of all the mRNAs in a cell. As part of this effort, the team will need to precisely quantify the exact nature of the chemical modifications that occur after transcription and establish how these modifications influence how mRNA interacts with tRNA and rRNA, and ultimately control protein levels.
This map, combined with other at the center, should lead to the identification of sites on the transcriptome that are modified in various tissues, and pinpoint how the differences in these modification patterns help to define variations in protein expression across tissue types, or distinguish a disease from normal tissue. Flagging those specific modification sites on the transcriptome will allow researchers to home in on targets for disrupting disease processes and regulating cell function.
The center has also created a system to map all the modifications that occur in rRNA and tRNA and explore how they recognize one another and interact to regulate protein expression. Data pertaining to modification of each of the three types of RNA will be synthesized into a unified view of gene expression regulation.
“Until now, researchers who study each of these types of RNA haven’t really talked to one another,” Jaffrey said. “They’re often very siloed, due to the specialized knowledge, approaches and even tools their work requires. The power of the center is to bring together people who are not ordinarily in communication with one another to use our combined expertise to understand this interaction of the three types of RNA, which is fundamental to making proteins.”