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==Human REXO2 exonuclease in complex with RNA.== | ==Human REXO2 exonuclease in complex with RNA.== | ||
<StructureSection load='6sty' size='340' side='right'caption='[[6sty]]' scene=''> | <StructureSection load='6sty' size='340' side='right'caption='[[6sty]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6STY FirstGlance]. <br> | <table><tr><td colspan='2'>[[6sty]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6STY FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sty OCA], [http://pdbe.org/6sty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sty RCSB], [http://www.ebi.ac.uk/pdbsum/6sty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sty ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">REXO2, SFN, SMFN, CGI-114 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sty OCA], [http://pdbe.org/6sty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sty RCSB], [http://www.ebi.ac.uk/pdbsum/6sty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sty ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/ORN_HUMAN ORN_HUMAN]] 3'-to-5' exoribonuclease specific for small oligoribonucleotides. Active on small (primarily </=5 nucleotides in length) single-stranded RNA and DNA oligomers. May have a role in cellular nucleotide recycling.<ref>PMID:23741365</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
RNA decay is a key element of mitochondrial RNA metabolism. To date, the only well-documented machinery that plays a role in mtRNA decay in humans is the complex of polynucleotide phosphorylase (PNPase) and SUV3 helicase, forming the degradosome. REXO2, a homolog of prokaryotic oligoribonucleases present in humans both in mitochondria and the cytoplasm, was earlier shown to be crucial for maintaining mitochondrial homeostasis, but its function in mitochondria has not been fully elucidated. In the present study, we created a cellular model that enables the clear dissection of mitochondrial and non-mitochondrial functions of human REXO2. We identified a novel mitochondrial short RNA, referred to as ncH2, that massively accumulated upon REXO2 silencing. ncH2 degradation occurred independently of the mitochondrial degradosome, strongly supporting the hypothesis that ncH2 is a primary substrate of REXO2. We also investigated the global impact of REXO2 depletion on mtRNA, revealing the importance of the protein for maintaining low steady-state levels of mitochondrial antisense transcripts and double-stranded RNA. Our detailed biochemical and structural studies provide evidence of sequence specificity of the REXO2 oligoribonuclease. We postulate that REXO2 plays dual roles in human mitochondria, 'scavenging' nanoRNAs that are produced by the degradosome and clearing short RNAs that are generated by RNA processing. | |||
Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA.,Szewczyk M, Malik D, Borowski LS, Czarnomska SD, Kotrys AV, Klosowska-Kosicka K, Nowotny M, Szczesny RJ Nucleic Acids Res. 2020 May 4. pii: 5828917. doi: 10.1093/nar/gkaa302. PMID:32365187<ref>PMID:32365187</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6sty" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Malik D]] | [[Category: Malik, D]] | ||
[[Category: Nowotny M]] | [[Category: Nowotny, M]] | ||
[[Category: Szczesny R]] | [[Category: Szczesny, R]] | ||
[[Category: Szewczyk M]] | [[Category: Szewczyk, M]] | ||
[[Category: 3'-5' exonuclease in complex with its rna substrate]] | |||
[[Category: Rna binding protein]] | |||
Revision as of 08:53, 13 May 2020
Human REXO2 exonuclease in complex with RNA.Human REXO2 exonuclease in complex with RNA.
Structural highlights
Function[ORN_HUMAN] 3'-to-5' exoribonuclease specific for small oligoribonucleotides. Active on small (primarily </=5 nucleotides in length) single-stranded RNA and DNA oligomers. May have a role in cellular nucleotide recycling.[1] Publication Abstract from PubMedRNA decay is a key element of mitochondrial RNA metabolism. To date, the only well-documented machinery that plays a role in mtRNA decay in humans is the complex of polynucleotide phosphorylase (PNPase) and SUV3 helicase, forming the degradosome. REXO2, a homolog of prokaryotic oligoribonucleases present in humans both in mitochondria and the cytoplasm, was earlier shown to be crucial for maintaining mitochondrial homeostasis, but its function in mitochondria has not been fully elucidated. In the present study, we created a cellular model that enables the clear dissection of mitochondrial and non-mitochondrial functions of human REXO2. We identified a novel mitochondrial short RNA, referred to as ncH2, that massively accumulated upon REXO2 silencing. ncH2 degradation occurred independently of the mitochondrial degradosome, strongly supporting the hypothesis that ncH2 is a primary substrate of REXO2. We also investigated the global impact of REXO2 depletion on mtRNA, revealing the importance of the protein for maintaining low steady-state levels of mitochondrial antisense transcripts and double-stranded RNA. Our detailed biochemical and structural studies provide evidence of sequence specificity of the REXO2 oligoribonuclease. We postulate that REXO2 plays dual roles in human mitochondria, 'scavenging' nanoRNAs that are produced by the degradosome and clearing short RNAs that are generated by RNA processing. Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA.,Szewczyk M, Malik D, Borowski LS, Czarnomska SD, Kotrys AV, Klosowska-Kosicka K, Nowotny M, Szczesny RJ Nucleic Acids Res. 2020 May 4. pii: 5828917. doi: 10.1093/nar/gkaa302. PMID:32365187[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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