Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Abstract

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.

p38 MAPK Regulates IL‐1β Induced IL‐6 Expression Through mRNA Stability in Osteoblasts

“…The signaling pathways that regulate ARE-directed mRNA decay have not been widely explored, and the relevant cis elements that mediate signal-induced mRNA stabilization have only started to be examined. In addition, mRNA stabilization may require cooperation between multiple RNA elements, suggesting that either proper mRNA folding is necessary for signal-induced stabilization or that interactions between different transacting factors can modulate AREdirected mRNA decay (2). Herein, we show that p38 MAPK decreases IL-1β-induced IL-6 gene expression by influencing mRNA stability, and also that a main target of this regulation is the 3′UTR of the IL-6 gene.…”

“…twenty different proteins which selectively bind to TNFα ARE mRNA in LPS-stimulated macrophages (48). Many of the proteins identified contain RNA recognition motifs (RRMs) and some of these were from the hnRNP A/B family which possess arginine/glycine rich domains known to be involved in protein-protein interactions as well as nuclear-cytoplasmic shuttling and RNA processing (2). One of the identified proteins, hnRNP A0 was identified as a downstream substrate of MAPKAPK2.…”

Expanding the ‘central dogma’: the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia

“…The steady-state concentration of mRNA is thought to be tightly regulated, although the mechanisms controlling mRNA concentration stability are not yet understood. 9,29 The tertiary structure of mRNA may impact its rate of degradation and translation. Some amino acids can be specified in the translation process by multiple RNA codons (eg CCU, CCC, CCA, and CCG all code for proline).…”

Sequence-optimised E2 constructs from BVDV-1b and BVDV-2 for DNA immunisation in cattle

“…This motif has been shown to confer rapid degradation to mammalian messenger RNA [5]. Putative polyadenylation signals were searched online with the POLYAH 1 programme.…”