5'-3' exoribonuclease 2 explained

5'-3' Exoribonuclease 2 (XRN2) also known as Dhm1-like protein is an exoribonuclease enzyme that in humans is encoded by the XRN2 gene.^[1]

The human gene encoding XRN2 shares similarity with the mouse Dhm1 and the yeast's Dhp1 (Schizosaccharomyces pombe) or RAT1 (Saccharomyces) genes. The yeast gene is involved in homologous recombination and RNA metabolism, such as RNA synthesis and RNA trafficking and termination.^[2] Complementation studies show that Dhm1 has a similar function in mouse as Dhp1.

Function

Human XRN2 is involved in the torpedo model of transcription termination.^[3]

The C. elegans homologue, XRN-2, is involved in the degradation of certain mature miRNAs and their dislodging from miRISC miRNAs.^[4]

In yeast, the Rat1 protein has been shown to also be involved in the torpedo transcription termination model. When a polyadenylation site has been detected on the nascent RNA and cleaved by the RNA polymerase II, the Rtt103 factor recruits Rat1 and attaches it to free end. The exonuclease activity of Rat1 degrades the RNA strand and halts transcriptions upon catching up to the polymerase.

See also

• Xrn1

Further reading

• Lehner B, Sanderson CM . A protein interaction framework for human mRNA degradation. . Genome Res. . 14 . 7 . 1315–23 . 2004 . 15231747 . 442147 . 10.1101/gr.2122004 .
• Deloukas P, Matthews LH, Ashurst J . The DNA sequence and comparative analysis of human chromosome 20. . Nature . 414 . 6866 . 865–71 . 2001. 11780052 . 10.1038/414865a . 2001Natur.414..865D . etal. free .
• Beausoleil SA, Villén J, Gerber SA . A probability-based approach for high-throughput protein phosphorylation analysis and site localization. . Nat. Biotechnol. . 24 . 10 . 1285–92 . 2006 . 16964243 . 10.1038/nbt1240 . 14294292 . etal.
• Lu Y, Liu P, James M . Genetic variants cis-regulating Xrn2 expression contribute to the risk of spontaneous lung tumor. . Oncogene . 29 . 7 . 1041–9 . 2010 . 19915612 . 6019621 . 10.1038/onc.2009.396 . etal.
• Lejeune F, Li X, Maquat LE . Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. . Mol. Cell . 12 . 3 . 675–87 . 2003 . 14527413 . 10.1016/S1097-2765(03)00349-6 . free .
• Wiemann S, Weil B, Wellenreuther R . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R . etal.
• Yang XC, Sullivan KD, Marzluff WF, Dominski Z . Studies of the 5' exonuclease and endonuclease activities of CPSF-73 in histone pre-mRNA processing. . Mol. Cell. Biol. . 29 . 1 . 31–42 . 2009 . 18955505 . 2612496 . 10.1128/MCB.00776-08 .
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . etal. free .
• Scherl A, Couté Y, Déon C . Functional proteomic analysis of human nucleolus. . Mol. Biol. Cell . 13 . 11 . 4100–9 . 2002 . 12429849 . 133617 . 10.1091/mbc.E02-05-0271 . etal.
• Kaneko S, Rozenblatt-Rosen O, Meyerson M, Manley JL . The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination. . Genes Dev. . 21 . 14 . 1779–89 . 2007 . 17639083 . 1920172 . 10.1101/gad.1565207 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 . etal.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Gromak N, West S, Proudfoot NJ . Pause sites promote transcriptional termination of mammalian RNA polymerase II. . Mol. Cell. Biol. . 26 . 10 . 3986–96 . 2006 . 16648491 . 1488997 . 10.1128/MCB.26.10.3986-3996.2006 .
• Andersen JS, Lam YW, Leung AK . Nucleolar proteome dynamics. . Nature . 433 . 7021 . 77–83 . 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 . etal.
• Li J, Zheng H, Ji C . A novel splice variant of human XRN2 gene is mainly expressed in blood leukocyte. . DNA Seq. . 16 . 2 . 143–6 . 2005 . 16147866 . 10.1080/10425170500066771 . 35865401 . etal.
• Mammalian Gene Collection Program Team . 4 . Strausberg . R. L. . Feingold . E. A. . Grouse . L. H. . Derge . J. G. . Klausner . R. D. . Collins . F. S. . Wagner . L. . Shenmen . C. M. . Schuler . G. D. . 10.1073/pnas.242603899 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . . 99 . 26 . 16899–16903 . 139241 . 2002 . 12477932. 2002PNAS...9916899M . free .
• Beausoleil SA, Jedrychowski M, Schwartz D . Large-scale characterization of HeLa cell nuclear phosphoproteins. . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–5 . 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . etal. free .

Notes and References

1. Zhang M, Yu L, Xin Y, Hu P, Fu Q, Yu C, Zhao S . Cloning and mapping of the XRN2 gene to human chromosome 20p11.1-p11.2 . Genomics . 59 . 2 . 252–4 . July 1999 . 10409438 . 10.1006/geno.1999.5866 .
2. David Tollervey . Termination by torpedo . Nature . 432 . 7016. 456–457 . November 2004 . 15565140. 10.1038/432456a . 6823163 .
3. West S, Gromak N, Proudfoot NJ . Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites . Nature . 432 . 7016 . 522–5 . November 2004 . 15565158 . 10.1038/nature03035 . 2004Natur.432..522W . 4365304 . free .
4. Chatterjee S, Grosshans H . Active turnover modulates mature microRNA activity in Caenorhabditis elegans . Nature . 461 . 7263 . 546–9 . September 2009 . 19734881 . 10.1038/nature08349 . 2009Natur.461..546C . 4414841 .