Exosome

The Exosome complex (or just- Exosome) is a multi-protein complex capable of degrading various types of RNA molecules. The Exosome complex is found in eukaryotic cell, and also in archaea, while in bacteria it is found as a simpler complex (but it has the same function). ^[1]

Some of the exosome components are:

• MTR3 and SKI6 are part of RNase PH domain-containing subunits proposed to form a central channel which threads RNA for degradation.
  
• MTR4 interacts with Nop53 and together they have a role in the maturation of 5.8S rRNA^[2].
  
• Rrp6 is a nuclear-specific subunit promoting cell survival during heat stress^[3].
  
• Rrp44 is the catalytic subunit ^[4].
  
• Csl4 is required for mRNA decay.
  
• M-phase phosphoprotein 6 is involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA.

Function

In order to see the structure of the protein complex, press .

Enzymatic function

The exosome is primarily a 3'-5' exoribonuclease, meaning that it degrades RNA molecules from their 3' end. In eukaryotes it also have an endoribonucleolytic function, meaning it cleaves RNA at sites within the molecule.

Substrates

The exosome is involved in the degradation and processing of a wide variety of RNA species. Substrates of the exosome include messenger RNA, ribosomal RNA, and many species of small RNAs.

Disease

Autoimmunity

The exosome complex is the target of autoantibodies, which are known to be found in people that suffer from various autoimmune diseases (especially PM/Scl overlap syndrome). In the autoimune diseases, antibodies are mainly directed against two of the proteins of the complex, called PM/Scl-100 and PM/Scl-75.

Cancer treatment

The Exosome is found to be inhibited by a cancer chemotherapy drug, which called antimetabolite fluorouracil. This drug is one of the most successful drugs for treating solid tumors.

Neurological disorders

Mutations in Exosome component 3 cause pontocerebellar hypoplasia and spinal motor neuron disease.

Structural highlights

The central machinery of exosome is shaped like a , with its RNA cleavage machinery sheltered in a groove inside. The core of the Exosome complex is made of a ring, which is consisting of six RNases proteins (Rnase PH-like proteins), and other proteins are attached. You can also view the complex in a .

3D structures of exosome

Exosome 3D structures