page_title: Exosome complex
section_title: Substrates
hierarchical_section_title: Exosome complex / Function / Substrates
caption_attribution_description: Two core subunits of the archaeal exosome complex, bound to U8 RNA. Based on crystal structure 2C37.
context_page_description: The exosome complex is a multi-protein intracellular complex capable of degrading various types of RNA molecules. Exosome complexes are found in both eukaryotic cells and archaea, while in bacteria a simpler complex called the degradosome carries out similar functions.
  The core of the exosome contains a six-membered ring structure to which other proteins are attached. In eukaryotic cells, the exosome complex is present in the cytoplasm, nucleus, and especially the nucleolus, although different proteins interact with the exosome complex in these compartments regulating the RNA degradation activity of the complex to substrates specific to these cell compartments. Substrates of the exosome include messenger RNA, ribosomal RNA, and many species of small RNAs. The exosome has an exoribonucleolytic function, meaning it degrades RNA starting at one end, and in eukaryotes also an endoribonucleolytic function, meaning it cleaves RNA at sites within the molecule.
  Several proteins in the exosome are the target of autoantibodies in patients with specific autoimmune diseases and some antimetabolic chemotherapies for cancer function by blocking the activity of the exosome.
context_section_description: The exosome is involved in the degradation and processing of a wide variety of RNA species. In the cytoplasm of cells, it is involved in the turn-over of messenger RNA (mRNA) molecules. The complex can degrade mRNA molecules that have been tagged for degradation because they contain errors, through interactions with proteins from the nonsense mediated decay or non-stop decay pathways. In alternative fashion, mRNAs are degraded as part of their normal turnover. Several proteins that stabilize or destabilize mRNA molecules through binding to AU-rich elements in the 3' untranslated region of mRNAs interact with the exosome complex. In the nucleus, the exosome is required for the correct processing of several small nuclear RNA molecules. Finally, the nucleolus is the compartment where the majority of the exosome complexes are found. There it plays a role in the processing of the 5.8S ribosomal RNA (the first identified function of the exosome) and of several small nucleolar RNAs.
  Although most cells have other enzymes that can degrade RNA, either from the 3' or from the 5' end of the RNA, the exosome complex is essential for cell survival. When the expression of exosome proteins is artificially reduced or stopped, for example by RNA interference, growth stops and the cells eventually die. Both the core proteins of the exosome complex, as well as the two main associated proteins, are essential proteins. Bacteria do not have an exosome complex; however, similar functions are performed by a simpler complex that includes the protein PNPase, called the degradosome.
  The exosome is a key complex in cellular RNA quality control. Unlike prokaryotes, eukaryotes possess highly active RNA surveillance systems that recognise unprocessed and mis-processed RNA-protein complexes (such as ribosomes) prior to their exit from the nucleus. It is presumed that this system prevents aberrant complexes from interfering with important cellular processes such as protein synthesis.
  In addition to RNA processing, turnover and surveillance activities, the exosome is important for the degradation of so-called cryptic unstable transcripts (CUTs) that are produced from thousands of loci within the yeast genome. The importance of these unstable RNAs and their degradation are still unclear, but similar RNA species have also been detected in human cells.
caption: Two core subunits of the archaeal exosome (Rrp41 and Rrp42), bound to a small RNA molecule (in red).
exif: {}