New discoveries have shown that although DNA sticks to “AGCT,” RNA contains modified nucleotides that “increases their vocabulary” past just their four letters, “AGCU.”
Before new discoveries of RNA nucleotide modifications were made, the focus of epigenetics studies was DNA and protein modifications. However, the discovery of what scientists are calling an “extra letter” brings RNA to the forefront of epigenetics studies, which they are now calling “epitranscriptomics.”
RNA has ten times as many nucleotide modifications as DNA because of its multiple functions with key players like mRNA, tRNA, and rRNA. DNA is considered to have just one main function, keeping the genetic information. This difference in functionality makes the ratio of nucleotide modifications make sense, but scientists believe that newly discovered nucleotide modifications could also be associated with disease states such as cancer and neurodegenerative disorders.
In their new paper published in Nature,
scientists Gidi Rechavi, PhD, from the Sheba Medical Center and Chuan He, PhD, from the University of Chicago co-led the study that discovered the newest nucleotide modification: methylation of position 1 of adenosine (m1A) in mRNA. The modification is significantly located at the beginning of protein translation and is strongly associated with protein synthesis.
Four years prior to this discovery, Rechavi’s group was the first to find another modification: methylation of position 6 of adenosine (m6A) in mRNA. Like m1A, this modification is specific to unique regions of mRNA. In addition, the modification is believed to respond to environmental stimuli.
Around the same time, He’s group identified an enzyme called FTO, for “fat mass and obesity associated,” to be able to remove the m6A marks from mRNA, illustrating that particular modification and potentially other modifications as a reversible process (NIH Genetics Home Reference). In addition to its role in RNA modification, FTO also has a role in both the nervous and cardiovascular systems and a “strong association” with body mass index, obesity risk, and type II diabetes (NIH Genetics Home Reference).
“This discovery further opens a window on a whole new world of biology for us to explore. These modifications have a major impact on almost every biological process.”
Source: American Friends of Tel Aviv University