New form of mRNA regulation characterized
RNA, once thought to be a mere
middleman between DNA and protein, is now recognized as the stage at which a
host of regulatory processes can act to allow for flexibility in gene
expression and thus the functions of cells and tissues.
In a new report in the journal Plant Cell, University of Pennsylvania biologists used material from both humans and plants to examine chemical modifications to messenger RNA, or mRNA, finding that the modifications appear to play a significant role in the process by which mRNAs either survive and become translated into protein or are targeted for degradation.
Their analyses
also revealed that mRNAs that encode proteins involved in responses to stress
were more likely than other mRNA molecules to be modified, a hint that the
modifications may provide a mechanism by which organisms can respond
dynamically, at the post-transcriptional level, when confronted with changes to
their environment.
The research was
led by Brian D. Gregory, an assistant professor in Penn's Department of Biology
in the School of Arts & Sciences, and Lee E. Vandivier, a graduate student
in Gregory's lab. Coauthors include Rafael Campos and Ian M. Silverman from the
Gregory lab, and Pavel P. Kuksa and Li-San Wang from Penn's Perelman School of
Medicine.
The snapshot of
all RNA sequences present in an organism at one time is known as the
transcriptome; in this study, researchers wanted to examine the
epitranscriptome, or modifications to the sequences of RNA molecules that may
go on to affect gene expression.
Gregory has
pioneered new techniques to investigate how RNA is regulated, including a
method that identifies the sites of interaction with RNA binding proteins,
called PIP-seq. In this study, he, Vandivier and colleagues used another
technique that Gregory and Wang together devised, called HAMR, for
high-throughput annotation of modified ribonucleotides. The approach allows for
the identification of nucleotides in RNA molecules that have been modified
after being transcribed from DNA.
"With these
changes you're increasing the potential chemical properties an RNA molecule can
have," Gregory said. "Instead of just having A, C, U and G, you have
almost every variation you can think of. "
Earlier work has
found more than 100 of these types of covalent modifications, primarily in RNA
molecules that do not code for proteins, such as transfer RNA and ribosomal
RNA.
