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Assembly of multicomponent machines in RNA metabolism: A common theme in mRNA decay pathways

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Abstract Multicomponent protein–RNA complexes comprising a ribonuclease and partner RNA helicase facilitate the turnover of mRNA in all domains of life. While these higher‐order complexes provide an effective means of physically and functionally coupling the processes of RNA remodeling and decay, most ribonucleases and RNA helicases do not exhibit sequence specificity in RNA binding. This raises the question as to how these assemblies select substrates for processing and how the activities are orchestrated at the precise moment to ensure efficient decay. The answers to these apparent puzzles lie in the auxiliary components of the assemblies that might relay decay‐triggering signals. Given their function within the assemblies, these components may be viewed as “sensors.” The functions and mechanisms of action of the sensor components in various degradation complexes in bacteria and eukaryotes are highlighted here to discuss their roles in RNA decay processes. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition
The Escherichia coli degradosome. A tetramer of the endoribonuclease RNase E (inset, one monomer shown in red) forms the scaffold of this degradosome. The C‐terminal unstructured tail of RNase E (red) acts as a binding platform for the helicase RhlB, the exoribonuclease/polymerase PNPase and the metabolic enzyme enolase, which acts as a sensor. The stem‐loop structure at the 3′‐end of the bacterial transcript is unwound and degraded by RhlB/PNPase. This figure is adapted from Carpousis (2007)
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An overview of the components of the eukaryotic degradosome‐like assemblies discussed above. The sensors in eukaryotes are more diverse and complex, which is reflected in the variety of the functions and the effects on RNA processing that these assemblies can mediate. The ribonuclease or the sensor component of the degradosome‐like assemblies in many UPF1‐mediated targeted mRNA decay pathways still remain unknown
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The exon junction complex (EJC) deposited at exon–exon junctions is displaced by the translating ribosome (top panel). However, presence of an EJC downstream of a stop codon identifies it as a premature termination codon (PTC). The EJC and associated factors act as the sensor component to signal nonsense‐mediated transcript decay (NMD) and trigger cooperative degradation (bottom panel). Assembly of the core NMD factors UPF3 and UPF2 on the EJC leads to recruitment of the RNA helicase UPF1, which in turn recruits the endoribonuclease SMG6
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Assembly of nuclear and cytoplasmic degradosome‐like complexes in eukaryotes. These assemblies are involved in RNA processing and surveillance in the nucleus and mRNA turnover in the cytoplasm. The nine structural components of the exosome, Exo9, assemble into a barrel in all eukaryotes other than plants. The helicases Mtr4 and Ski2 associate with the nuclear and cytoplasmic exosomes respectively, via different scaffolding factors (Mpp6, Rrp47/Rrp6 in the nucleus and Ski7 and Ski3‐Ski8 in the cytoplasm). The helicase‐exosome assemblies contact the sensor components (the AIM‐containing proteins in the nucleus, and the ribosome stalled on an mRNA or the Ska1 protein bound to an untranslated RNA in the cytoplasm) via their respective arch domains to build up a degradosome and mediate decay. This figure is adapted from Makino, Halbach, and Conti (2013) and Lingaraju, Johnsen, et al. (2019)
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Mitochondrial exoribonuclease complexes (mtEXO) in yeast and humans. The conserved Suv3 helicase associates with the exoribonuclease Dss1 in most species, other than in humans where it engages PNPase. The sensors of the yeast and human mtEXO differ, suggesting different functional roles for these assemblies in the two species. Sensors of human mtEXO also vary depending on the nature of the RNA species targeted for degradation (the transcription machinery for most RNA species including mRNA, and GRSF1 for non‐coding RNAs rich in G‐quadruplexes)
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An overview of the ribonucleases, helicases, and sensor components that make up prototype degradosomes in different species of bacteria. While metabolic enzymes are the typical sensors of the bacterial degradosome, the RNA chaperone Hfq and its associated sRNA as well as the translating ribosome have also been shown to be associated with degradosomes in certain cases
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RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms
RNA Turnover and Surveillance > Regulation of RNA Stability

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