| Structural highlights
Function
[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.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Trf4/5p-Air1/2p-Mtr4p polyadenylation complex (TRAMP) is an essential component of nuclear RNA surveillance in yeast. It recognizes a variety of nuclear transcripts produced by all three RNA polymerases, adds short poly(A) tails to aberrant or unstable RNAs and activates the exosome for their degradation. Despite the advances in understanding the structural features of the isolated complex subunits or their fragments, the details of complex assembly, RNA recognition and exosome activation remain poorly understood. Here we provide the first understanding of the RNA binding mode of the complex. We show that Air2p is an RNA-binding subunit of TRAMP. We identify the zinc knuckles (ZnK) 2, 3 and 4 as the RNA-binding domains, and reveal the essentiality of ZnK4 for TRAMP4 polyadenylation activity. Furthermore, we identify Air2p as the key component of TRAMP4 assembly providing bridging between Mtr4p and Trf4p. The former is bound via the N-terminus of Air2p, while the latter is bound via ZnK5, the linker between ZnK4 and 5 and the C-terminus of the protein. Finally, we uncover the RNA binding part of the Mtr4p arch, the KOW domain, as the essential component for TRAMP-mediated exosome activation.
Air2p is critical for the assembly and RNA-binding of the TRAMP complex and the KOW domain of Mtr4p is crucial for exosome activation.,Holub P, Lalakova J, Cerna H, Pasulka J, Sarazova M, Hrazdilova K, Arce MS, Hobor F, Stefl R, Vanacova S Nucleic Acids Res. 2012 Mar 8. PMID:22402490[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Holub P, Lalakova J, Cerna H, Pasulka J, Sarazova M, Hrazdilova K, Arce MS, Hobor F, Stefl R, Vanacova S. Air2p is critical for the assembly and RNA-binding of the TRAMP complex and the KOW domain of Mtr4p is crucial for exosome activation. Nucleic Acids Res. 2012 Mar 8. PMID:22402490 doi:10.1093/nar/gks223
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