Post-transcriptional regulation of gene expression by degradation of messenger RNAs.
Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.
Bevilacqua
Annamaria
A
Department of Pharmacology, University of Milan, Italy.
Ceriani
Maria Cristina
MC
Capaccioli
Sergio
S
Nicolin
Angelo
A
D000818:Animals; D016503:Drug Delivery Systems; D005095:Exoribonucleases / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008957:Models, Genetic; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid
D046911:Macromolecular Substances; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005095:Exoribonucleases