Coordination of gene expression on the post-transcriptional level by RNA-binding proteins and small noncoding RNAs.
The Keene lab devised methods to identify structurally and functionally related cellular mRNAs and microRNAs that cluster together based upon their association with ELAV/Hu RBPs and other RNA-binding proteins. This general approach has been termed ribonomics because it uses microarrays or Solexa sequencing to determine mRNAs and microRNAs associated with ribonucleoprotein complexes. This novel approach to functional genomics is has been used and adapted in many laboratories to analyze biological responses such as virus infectivity, tumorigenesis, genotoxic agents, radiation and developmental inducers. These studies have revealed that functionally related mRNA subsets are post-transcriptionally coordinated, thereby, representing the organizational state of genetic information between the genome and the proteome. Based on these findings, Keene proposed the concept of Post-Transcriptional RNA Operons and Regulons (PTRO) based upon the combinatorial regulation of mRNAs at all steps between transcription and translation, potentially revealing a RNP-regulatory code or “USER-code”. The PTRO is a simplifying model that explains the organization and dynamic properties of multiple mRNA and noncoding RNAs located in the nucleus and cytoplasm. Many dozens of PTROs have since been reported in archaea, yeasts, worms, flies, trypanosomes, plants, humans and other mammals, and unexpectedly, in bacteria. The PTRO model has a variety of therapeutic implications as it can be used to identify dynamic changes in time and space of all cellular mRNAs and noncoding RNAs involved in growth regulation, neuronal plasticity, immune regulation and cancer.