Exosome Complex


A living cell consists in a dynamic equilibrium of many opposing processes. Steady‐state levels of all ribonucleic acid (RNA) and protein molecules result from a specific balance between constant production and ongoing decay. RNA degradation is thus of paramount importance for the cell's wellbeing. A major player in this process is the exosome complex. It is a multisubunit entity endowed with ribonuclease activities. It is highly conserved in evolution, found in all Eukaryota and most Archaea; Eubacteria lack the exosome but they do have a very similar enzyme. The eukaryotic exosome has endo‐ and exoribonuclease activity and it engages a plethora of substrates in numerous pathways of RNA decay, RNA processing and RNA surveillance. Substrate specificity is conferred by a wide range of cofactors, some of them multisubunit complexes with interaction networks of their own.

Key Concepts:

  • The exosome core is a conserved protein complex.

  • Exosomes of Archaea and Eukaryota have different enzymatic activities.

  • Catalytic activity in eukaryotic exosomes comes from noncore subunits.

  • Catalytic subunits are organised differently in yeast, plants and mammals.

  • The exosome participates in RNA decay, processing and surveillance.

  • Many cofactors are responsible for recruiting substrates to the exosome.

Keywords: exosome; ribonuclease activity; RNA degradation; RNA processing; RNA surveillance; TRAMP complex

Figure 1.

Structure of the exosome. (a, b) Crystal structure of the human exosome core (2NN6) viewed from the side (a) and the top (b), and crystal structures of human Rrp6 (3SAF, top) and yeast Dis3 (2WP8, bottom) with catalytic residues marked in red. (c) Schematic representation of the eukaryotic exosome core as viewed from the top side, down the central channel. Subunits are colour‐coded: Rrp41‐like in blue, Rrp42‐like in yellow and cap proteins in purple. Dimers of hexamer subunits are: Rrp41‐Rrp45, Rrp46‐Rrp43 and Mtr3‐Rrp42. (d) Threading of a single‐stranded 3′ end of a structured RNA molecule through the exosome core and on to the catalytic site of the RNB domain of Dis3.

Figure 2.

Composition and subcellular localisation of the exosome complex in various organisms. (a) The archaeal exosome core has three active subunits and a variable composition of the cap and it is tethered to the cell membrane by DnaG. (b) The inactive core of the yeast exosome is present throughout the cell. Dis3 interacts with the core in the nucleoplasm, the nucleolus and the cytoplasm, whereas Rrp6 is restricted to the nucleus. (c) The human core is also inactive and present throughout the cell. DIS3 is mostly nuclear, but small quantities are found in the cytoplasm, and DIS3L is strictly cytoplasmic. RRP6 is found in all three compartments. (d) In plants the Rrp6‐like proteins are differentially distributed: AtRRP6L3 is restricted to the cytoplasm, AtRRP6L1 – to the nucleoplasm and AtRRP6L2 is found in the nucleoplasm and the nucleolus. The localisation of core proteins and AtDIS3 is presumably the same as in other eukaryotes but not confirmed.



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Further Reading

Chlebowski A, Tomecki R, Lopez ME, Seraphin B and Dziembowski A (2011) Catalytic properties of the eukaryotic exosome. Advances in Experimental Medicine and Biology 702: 63–78.

Clayton C and Estevez A (2011) The exosomes of trypanosomes and other protists. Advances in Experimental Medicine and Biology 702: 39–49.

Coy S and Vasiljeva L (2011) The exosome and heterochromatin: multilevel regulation of gene silencing. Advances in Experimental Medicine and Biology 702: 105–121.

Evguenieva‐Hackenberg E (2011) The archaeal exosome. Advances in Experimental Medicine and Biology 702: 29–38.

Januszyk K and Lima CD (2011) Structural components and architectures of RNA exosomes. Advances in Experimental Medicine and Biology 702: 9–28.

Lange H and Gagliardi D (2011) The exosome and 3′‐5′ RNA degradation in plants. Advances in Experimental Medicine and Biology 702: 50–62.

Mitchell P and Tollervey D (2011) Finding the exosome. Advances in Experimental Medicine and Biology 702: 1–8.

Rougemaille M and Libri D (2011) Control of cryptic transcription in eukaryotes. Advances in Experimental Medicine and Biology 702: 122–131.

Schaeffer D, Clark A, Klauer AA, Tsanova B and van Hoof A (2011) Functions of the cytoplasmic exosome. Advances in Experimental Medicine and Biology 702: 79–90.

Staals RH and Pruijn GJ (2011) The human exosome and disease. Advances in Experimental Medicine and Biology 702: 132–142.

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Chlebowski, Aleksander, and Dziembowski, Andrzej(Jul 2012) Exosome Complex. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024052]