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==Exosome==  
==Exosome==  
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='2je6' size='340' side='right' caption='Exosome complex containing exonuclease 1 (green), exonuclease 2 (grey) and exosome complex RNA-binding protein 1 (wheat) complex with PEG400 (pdb code [[2je6]]).' scene=''>
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 in a simpler complex (but it has the same function). <ref>http://en.wikipedia.org/wiki/Exosome_complex#Structure</ref>
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). <ref>http://en.wikipedia.org/wiki/Exosome_complex#Structure</ref>
 
Some of the exosome components are:<br />
*'''MTR3''' and '''SKI6''' are part of RNase PH domain-containing subunits proposed to form a central channel which threads RNA for degradation.<br />
*'''MTR4''' interacts with Nop53 and together they have a role in the maturation of 5.8S rRNA<ref>PMID:28883156</ref>.<br />
*'''Rrp6''' is a nuclear-specific subunit promoting cell survival during heat stress<ref>PMID:32521279</ref>.<br />
*'''Rrp44''' is the catalytic subunit <ref>PMID:19060898</ref>.<br />
*'''Csl4''' is required for mRNA decay.<br />
*'''M-phase phosphoprotein 6''' is involved in the 3'-processing  of the 7S pre-RNA to the mature 5.8S rRNA.
 
__TOC__


== Function ==
== Function ==
<scene name='60/609824/2nn6/8'>Exosome</scene>
In order to see the structure of the protein complex, press <scene name='60/609824/2nn6/8'>Exosome</scene>.
 
===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 ==
== Disease ==
'''Autoimmunity'''
===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.
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'''
===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.
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 ==
== Structural highlights ==
The core of the Exosom complex is made of a ring, which consisting of six RNases proteins (Rnase PH-like proteins).
The central machinery of exosome is shaped like a <scene name="/12/3456/Sample/1">barrel</scene>, with its RNA cleavage machinery sheltered in a groove inside.
<scene name="/12/3456/Sample/1">1</scene><scene name="/12/3456/Sample/2">2</scene>
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 <scene name="/12/3456/Sample/2">ribbon view</scene>.
 
==3D structures of exosome==
[[Exosome 3D structures]]


</StructureSection>
</StructureSection>
== References ==
== References ==
<references/>
<references/>
[[Category: Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Nitzan Dubovski, Michal Harel