| Structural highlights
Function
XRN2_YEAST Possesses 5'->3' exoribonuclease activity. Required for the processing of nuclear mRNA, rRNA and small nucleolar RNA (snoRNA) precursors. May promote termination of transcription by RNA polymerase II via the recruitment of 3'-end processing factors to the poly(A) site and by the degradation of nascent RNA downstream of the poly(A) site.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
Publication Abstract from PubMed
The Rat1 5'-3' exoribonuclease together with its partner Rai1 have important roles in Saccharomyces cerevisiae RNA polymerase II transcription termination. Rtt103 copurifies with Rat1-Rai1 in S. cerevisiae, but its mechanism of interaction with them is not known. We report here the cryo-EM structure of the S. cerevisiae Rat1-Rai1-Rtt103 ternary complex at 2.9 A resolution. We found that a short segment of Rtt103 is in close contact with Rai1, while the rest of Rtt103, including its RNA polymerase II C-terminal domain interaction domain, shows no interactions with Rai1 or Rat1. This is in contrast to the observations on the Komagataella phaffii Rat1-Rai1-Rtt103 complex, where only the RNA polymerase II C-terminal domain interaction domain of Rtt103 has contacts with Rai1. Our structure reveals that S. cerevisiae Rtt103 Pro261 and Tyr263 have important contacts with Rai1, and we show that the P261G/Y263A mutation of Rtt103 blocks the interaction with Rat1-Rai1. Our structure suggests that, in yeast, this segment of Rtt103, which we have named the Rai1 interaction segment, likely helps the recruitment of Rat1-Rai1 to RNA polymerase II for termination.
Molecular basis for the interaction between Saccharomyces cerevisiae Rtt103 and the Rat1-Rai1 complex.,Chu HF, Tong L Nat Commun. 2025 Apr 5;16(1):3266. doi: 10.1038/s41467-025-58671-z. PMID:40188244[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xue Y, Bai X, Lee I, Kallstrom G, Ho J, Brown J, Stevens A, Johnson AW. Saccharomyces cerevisiae RAI1 (YGL246c) is homologous to human DOM3Z and encodes a protein that binds the nuclear exoribonuclease Rat1p. Mol Cell Biol. 2000 Jun;20(11):4006-15. PMID:10805743 doi:10.1128/MCB.20.11.4006-4015.2000
- ↑ Bousquet-Antonelli C, Presutti C, Tollervey D. Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell. 2000 Sep 15;102(6):765-75. PMID:11030620 doi:10.1016/s0092-8674(00)00065-9
- ↑ Geerlings TH, Vos JC, Raue HA. The final step in the formation of 25S rRNA in Saccharomyces cerevisiae is performed by 5'-->3' exonucleases. RNA. 2000 Dec;6(12):1698-703. PMID:11142370
- ↑ He F, Jacobson A. Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs. Mol Cell Biol. 2001 Mar;21(5):1515-30. PMID:11238889 doi:http://dx.doi.org/10.1128/MCB.21.5.1515-1530.2001
- ↑ Danin-Kreiselman M, Lee CY, Chanfreau G. RNAse III-mediated degradation of unspliced pre-mRNAs and lariat introns. Mol Cell. 2003 May;11(5):1279-89. PMID:12769851 doi:10.1016/s1097-2765(03)00137-0
- ↑ Lee CY, Lee A, Chanfreau G. The roles of endonucleolytic cleavage and exonucleolytic digestion in the 5'-end processing of S. cerevisiae box C/D snoRNAs. RNA. 2003 Nov;9(11):1362-70. PMID:14561886
- ↑ Kim M, Krogan NJ, Vasiljeva L, Rando OJ, Nedea E, Greenblatt JF, Buratowski S. The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II. Nature. 2004 Nov 25;432(7016):517-22. PMID:15565157 doi:http://dx.doi.org/nature03041
- ↑ Fang F, Phillips S, Butler JS. Rat1p and Rai1p function with the nuclear exosome in the processing and degradation of rRNA precursors. RNA. 2005 Oct;11(10):1571-8. PMID:16131592 doi:10.1261/rna.2900205
- ↑ Luo W, Johnson AW, Bentley DL. The role of Rat1 in coupling mRNA 3'-end processing to transcription termination: implications for a unified allosteric-torpedo model. Genes Dev. 2006 Apr 15;20(8):954-65. PMID:16598041 doi:10.1101/gad.1409106
- ↑ Stevens A, Poole TL. 5'-exonuclease-2 of Saccharomyces cerevisiae. Purification and features of ribonuclease activity with comparison to 5'-exonuclease-1. J Biol Chem. 1995 Jul 7;270(27):16063-9. PMID:7608167 doi:10.1074/jbc.270.27.16063
- ↑ Kenna M, Stevens A, McCammon M, Douglas MG. An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity. Mol Cell Biol. 1993 Jan;13(1):341-50. PMID:8417335 doi:10.1128/mcb.13.1.341-350.1993
- ↑ Poole TL, Stevens A. Structural modifications of RNA influence the 5' exoribonucleolytic hydrolysis by XRN1 and HKE1 of Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1997 Jun 27;235(3):799-805. PMID:9207242 doi:10.1006/bbrc.1997.6877
- ↑ Dichtl B, Stevens A, Tollervey D. Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes. EMBO J. 1997 Dec 1;16(23):7184-95. PMID:9384595 doi:10.1093/emboj/16.23.7184
- ↑ Petfalski E, Dandekar T, Henry Y, Tollervey D. Processing of the precursors to small nucleolar RNAs and rRNAs requires common components. Mol Cell Biol. 1998 Mar;18(3):1181-9. PMID:9488433
- ↑ Villa T, Ceradini F, Presutti C, Bozzoni I. Processing of the intron-encoded U18 small nucleolar RNA in the yeast Mol Cell Biol. 1998 Jun;18(6):3376-83. PMID:9584178 doi:10.1128/MCB.18.6.3376
- ↑ Qu LH, Henras A, Lu YJ, Zhou H, Zhou WX, Zhu YQ, Zhao J, Henry Y, Caizergues-Ferrer M, Bachellerie JP. Seven novel methylation guide small nucleolar RNAs are processed from a common polycistronic transcript by Rat1p and RNase III in yeast. Mol Cell Biol. 1999 Feb;19(2):1144-58. PMID:9891049 doi:10.1128/MCB.19.2.1144
- ↑ Chu HF, Tong L. Molecular basis for the interaction between Saccharomyces cerevisiae Rtt103 and the Rat1-Rai1 complex. Nat Commun. 2025 Apr 5;16(1):3266. PMID:40188244 doi:10.1038/s41467-025-58671-z
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