9g8n

Structural highlights

Function

EXOS4_HUMAN Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC4 binds to ARE-containing RNAs.^{[1] [2] [3] [4] [5]}

References

1. ↑ Anderson JR, Mukherjee D, Muthukumaraswamy K, Moraes KC, Wilusz CJ, Wilusz J. Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome. RNA. 2006 Oct;12(10):1810-6. Epub 2006 Aug 15. PMID:16912217 doi:10.1261/rna.144606
2. ↑ van Dijk EL, Schilders G, Pruijn GJ. Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA. 2007 Jul;13(7):1027-35. Epub 2007 Jun 1. PMID:17545563 doi:10.1261/rna.575107
3. ↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
4. ↑ Slomovic S, Fremder E, Staals RH, Pruijn GJ, Schuster G. Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7407-12. doi:, 10.1073/pnas.0910621107. Epub 2010 Apr 5. PMID:20368444 doi:10.1073/pnas.0910621107
5. ↑ Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell. 2011 Feb 4;144(3):353-63. doi: 10.1016/j.cell.2011.01.001. Epub 2011 Jan, 20. PMID:21255825 doi:10.1016/j.cell.2011.01.001