How genes get ‘switched on’ has fascinated scientists for decades, but equally important questions about how they are ‘turned off’ have been largely overlooked.
As the messengers carrying instructions from DNA for the creation of proteins, the formation and decay of cellular RNAs is critical to maintaining cell stability and regulation – and of direct bearing on how our immune systems respond to disease.
Researchers at the Yale Chemical Biology Institute have begun to untangle the complex pathways used by RNAs and the biological processes that they regulate.
Published today in the journal Cell Chemical Biology, the scientists reveal a new biological tool to help pinpoint numerous specific RNA “depletion” pathways and associated protein complexes.
Masked by alternative decay pathways, singling out the effects of RNA decay from single enzymes has posed a challenge to traditional studies of gene function.
To complement previous approaches, Vicky Luo, the study’s first author and a former graduate student, applied a novel chemical inhibitor of a major human RNA decay enzyme, DCP2, to expand the list of its regulated, target genes, including specific RNA messengers involved in the transcription of important proteins.
Such chemical tools are providing new insights into regulatory pathways in human cells and previously undruggable diseases shielded from would-be treatments.
The study’s senior author is Sarah Slavoff, Assistant Professor of Chemistry and of Molecular Biophysics and Biochemistry.
By Jon Atherton