| Structural highlights
Function
[PAP2_YEAST] Catalytic subunit of the TRAMP complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism limiting inappropriate expression of genetic information. Polyadenylation is required for the degradative activity of the exosome on several of its nuclear RNA substrates like cryptic transcripts generated by RNA polymerase II and III, or hypomethylated pre-tRNAi-Met. Polyadenylates RNA processing and degradation intermediates of snRNAs, snoRNAs and mRNAs that accumulate in strains lacking a functional exosome. TRF4 is also required for proper nuclear division in mitosis, DNA damage repair and sister chromatid cohesion. Involved in the regulation of histone mRNA levels. May mediate mitotic chromosome condensation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [AIR2_YEAST] Component of the TRAMP (TRF4) complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism limiting inappropriate expression of genetic information. Polyadenylation is required for the degradative activity of the exosome on several of its nuclear RNA substrates like cryptic transcripts generated by RNA polymerase II and III, or hypomethylated pre-tRNAi-Met. Both complexes polyadenylate RNA processing and degradation intermediates of snRNAs, snoRNAs and mRNAs that accumulate in strains lacking a functional exosome. AIR2 also inhibits the methylation of NPL3 mediated by HMT1 through its interaction with HMT1.[18] [19] [20] [21] [22]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex recognizes aberrant RNAs in Saccharomyces cerevisiae and targets them for degradation. A TRAMP subcomplex consisting of a noncanonical poly(A) RNA polymerase in the Pol ss superfamily of nucleotidyl transferases, Trf4p, and a zinc knuckle protein, Air2p, mediates initial substrate recognition. Trf4p and related eukaryotic poly(A) and poly(U) polymerases differ from other characterized enzymes in the Pol ss superfamily both in sequence and in the lack of recognizable nucleic acid binding motifs. Here we report, at 2.7-A resolution, the structure of Trf4p in complex with a fragment of Air2p comprising two zinc knuckle motifs. Trf4p consists of a catalytic and central domain similar in fold to those of other noncanonical Pol beta RNA polymerases, and the two zinc knuckle motifs of Air2p interact with the Trf4p central domain. The interaction surface on Trf4p is highly conserved across eukaryotes, providing evidence that the Trf4p/Air2p complex is conserved in higher eukaryotes as well as in yeast and that the TRAMP complex may also function in RNA surveillance in higher eukaryotes. We show that Air2p, and in particular sequences encompassing a zinc knuckle motif near its N terminus, modulate Trf4p activity, and we present data supporting a role for this zinc knuckle in RNA binding. Finally, we show that the RNA 3' end plays a role in substrate recognition.
Structure and function of the polymerase core of TRAMP, a RNA surveillance complex.,Hamill S, Wolin SL, Reinisch KM Proc Natl Acad Sci U S A. 2010 Aug 9. PMID:20696927[23]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sadoff BU, Heath-Pagliuso S, Castano IB, Zhu Y, Kieff FS, Christman MF. Isolation of mutants of Saccharomyces cerevisiae requiring DNA topoisomerase I. Genetics. 1995 Oct;141(2):465-79. PMID:8647385
- ↑ Castano IB, Brzoska PM, Sadoff BU, Chen H, Christman MF. Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae. Genes Dev. 1996 Oct 15;10(20):2564-76. PMID:8895658
- ↑ Castano IB, Heath-Pagliuso S, Sadoff BU, Fitzhugh DJ, Christman MF. A novel family of TRF (DNA topoisomerase I-related function) genes required for proper nuclear segregation. Nucleic Acids Res. 1996 Jun 15;24(12):2404-10. PMID:8710513
- ↑ Walowsky C, Fitzhugh DJ, Castano IB, Ju JY, Levin NA, Christman MF. The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. J Biol Chem. 1999 Mar 12;274(11):7302-8. PMID:10066793
- ↑ Wang Z, Castano IB, De Las Penas A, Adams C, Christman MF. Pol kappa: A DNA polymerase required for sister chromatid cohesion. Science. 2000 Aug 4;289(5480):774-9. PMID:10926539
- ↑ Saitoh S, Chabes A, McDonald WH, Thelander L, Yates JR, Russell P. Cid13 is a cytoplasmic poly(A) polymerase that regulates ribonucleotide reductase mRNA. Cell. 2002 May 31;109(5):563-73. PMID:12062100
- ↑ Wang Z, Castano IB, Adams C, Vu C, Fitzhugh D, Christman MF. Structure/function analysis of the Saccharomyces cerevisiae Trf4/Pol sigma DNA polymerase. Genetics. 2002 Feb;160(2):381-91. PMID:11861546
- ↑ Edwards S, Li CM, Levy DL, Brown J, Snow PM, Campbell JL. Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion. Mol Cell Biol. 2003 Apr;23(8):2733-48. PMID:12665575
- ↑ Kadaba S, Krueger A, Trice T, Krecic AM, Hinnebusch AG, Anderson J. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 2004 Jun 1;18(11):1227-40. Epub 2004 May 14. PMID:15145828 doi:http://dx.doi.org/10.1101/gad.1183804
- ↑ LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, Tollervey D. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell. 2005 Jun 3;121(5):713-24. PMID:15935758 doi:http://dx.doi.org/S0092-8674(05)00442-3
- ↑ Wyers F, Rougemaille M, Badis G, Rousselle JC, Dufour ME, Boulay J, Regnault B, Devaux F, Namane A, Seraphin B, Libri D, Jacquier A. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell. 2005 Jun 3;121(5):725-37. PMID:15935759 doi:http://dx.doi.org/S0092-8674(05)00443-5
- ↑ Haracska L, Johnson RE, Prakash L, Prakash S. Trf4 and Trf5 proteins of Saccharomyces cerevisiae exhibit poly(A) RNA polymerase activity but no DNA polymerase activity. Mol Cell Biol. 2005 Nov;25(22):10183-9. PMID:16260630 doi:http://dx.doi.org/25/22/10183
- ↑ Vanacova S, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, Langen H, Keith G, Keller W. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 2005 Jun;3(6):e189. Epub 2005 Apr 19. PMID:15828860 doi:http://dx.doi.org/05-PLBI-RA-0095R2
- ↑ Egecioglu DE, Henras AK, Chanfreau GF. Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA. 2006 Jan;12(1):26-32. PMID:16373491 doi:http://dx.doi.org/10.1261/rna.2207206
- ↑ Kadaba S, Wang X, Anderson JT. Nuclear RNA surveillance in Saccharomyces cerevisiae: Trf4p-dependent polyadenylation of nascent hypomethylated tRNA and an aberrant form of 5S rRNA. RNA. 2006 Mar;12(3):508-21. Epub 2006 Jan 23. PMID:16431988 doi:http://dx.doi.org/rna.2305406
- ↑ Reis CC, Campbell JL. Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae. Genetics. 2007 Mar;175(3):993-1010. Epub 2006 Dec 18. PMID:17179095 doi:http://dx.doi.org/genetics.106.065987
- ↑ Hamill S, Wolin SL, Reinisch KM. Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proc Natl Acad Sci U S A. 2010 Aug 9. PMID:20696927
- ↑ Inoue K, Mizuno T, Wada K, Hagiwara M. Novel RING finger proteins, Air1p and Air2p, interact with Hmt1p and inhibit the arginine methylation of Npl3p. J Biol Chem. 2000 Oct 20;275(42):32793-9. PMID:10896665 doi:http://dx.doi.org/10.1074/jbc.M004560200
- ↑ LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, Tollervey D. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell. 2005 Jun 3;121(5):713-24. PMID:15935758 doi:http://dx.doi.org/S0092-8674(05)00442-3
- ↑ Wyers F, Rougemaille M, Badis G, Rousselle JC, Dufour ME, Boulay J, Regnault B, Devaux F, Namane A, Seraphin B, Libri D, Jacquier A. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell. 2005 Jun 3;121(5):725-37. PMID:15935759 doi:http://dx.doi.org/S0092-8674(05)00443-5
- ↑ Vanacova S, Wolf J, Martin G, Blank D, Dettwiler S, Friedlein A, Langen H, Keith G, Keller W. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 2005 Jun;3(6):e189. Epub 2005 Apr 19. PMID:15828860 doi:http://dx.doi.org/05-PLBI-RA-0095R2
- ↑ Hamill S, Wolin SL, Reinisch KM. Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proc Natl Acad Sci U S A. 2010 Aug 9. PMID:20696927
- ↑ Hamill S, Wolin SL, Reinisch KM. Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proc Natl Acad Sci U S A. 2010 Aug 9. PMID:20696927
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