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Mod5 Protein Binds to Trna Gene Complexes and Affects Local

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Mod5 Protein Binds to Trna Gene Complexes and Affects Local Correction and Retractions CORRECTION BIOCHEMISTRY Correction for “Mod5 protein binds to tRNA gene complexes and issue 33, August 13, 2013, of Proc Natl Acad Sci USA (110: affects local transcriptional silencing,” by Matthew Pratt-Hyatt, E3081–E3089; first published July 29, 2013;10.1073/pnas. Dave A. Pai, Rebecca A. Haeusler, Glenn G. Wozniak, Paul D. 1219946110). Good, Erin L. Miller, Ian X. McLeod, John R. Yates III, The authors note that Fig. 5 appeared incorrectly. The cor- Anita K. Hopper, and David R. Engelke, which appeared in rected figure and its legend appear below. A ATG/GTP binding site S. cerevisiae H. sapiens A. thaliana S. cerevisiae H. sapiens A. thaliana S. cerevisiae H. sapiens A. thaliana RETRACTIONS CORRECTION AND DMAPP binding site S. cerevisiae H. sapiens A. thaliana S. cerevisiae H. sapiens A. thaliana Zn-Finger motif S. cerevisiae H. sapiens A. thaliana S. cerevisiae H. sapiens A. thaliana B +His -His mod5Δ S. cerevisiae A. thaliana H. sapiens Fig. 5. Conservation of the Mod5 protein and silencing function in eukaryotes. (A) The alignment of three Mod5 proteins from S. cerevisiae, A. thaliana,and H. sapiens is depicted, with areas of conservation indicated by shaded boxes. All variants contain motifs for ATP/GTP binding and DMAPP binding, including E. coli (14, 40). Eukaryotic homologs also have a zinc finger motif in the C-terminal extensions. (B) tgm silencing functions of yeast Mod5 are conserved in plant and human proteins. It was previously shown that human and Arabidopsis Mod5 homologs are able to restore i6A modification of tRNAs in yeast in an mod5Δ strain (14, 24). Plasmids expressing these ORFs were tested for supporting tgm silencing in an mod5Δ strain containing a tgm silencing reporter plasmid, with loss of silencing shown by growth on media lacking histidine (−His). Although both homologs restore silencing, the H. sapiens version of Mod5 (TRIT1) is consistently more robust in preventing growth without histidine. www.pnas.org/cgi/doi/10.1073/pnas.1400058111 www.pnas.org PNAS | February 11, 2014 | vol. 111 | no. 6 | 2397–2398 Downloaded by guest on September 29, 2021 RETRACTIONS CELL BIOLOGY CELL BIOLOGY Retraction for “Distinct function of 2 chromatin remodeling Retraction for “Testis-specific protein on Y chromosome (TSPY) complexes that share a common subunit, Williams syndrome represses the activity of the androgen receptor in androgen- transcription factor (WSTF),” by Kimihiro Yoshimura, Hirochika dependent testicular germ-cell tumors,” by Chihiro Akimoto, Kitagawa, Ryoji Fujiki, Masahiko Tanabe, Shinichiro Takezawa, Takashi Ueda, Kazuki Inoue, Ikuko Yamaoka, Matomo Sakari, Ichiro Takada, Ikuko Yamaoka, Masayoshi Yonezawa, Takeshi Wataru Obara, Tomoaki Fujioka, Akira Nagahara, Norio Kondo, Yoshiyuki Furutani, Hisato Yagi, Shin Yoshinaga, Takeyoshi Nonomura, Syuichi Tsutsumi, Hiroyuki Aburatani, Tsuneharu Masuda, Toru Fukuda, Yoko Yamamoto, Kanae Ebihara, Dean Y. Miki, Takahiro Matsumoto, Hirochika Kitagawa, and Shigeaki Li, Rumiko Matsuoka, Jun K. Takeuchi, Takahiro Matsumoto, Kato, which appeared in issue 46, November 16, 2010, of Proc and Shigeaki Kato, which appeared in issue 23, June 9, 2009, of Natl Acad Sci USA (107:19891–19896; first published November Proc Natl Acad Sci USA (106:9280–9285; first published May 26, 1, 2010; 10.1073/pnas.1010307107). 2009; 10.1073/pnas.0901184106). The authors wish to note, “Recently it has come to our at- The authors note, “Recently it has come to our attention that tention that inappropriate data arrangements and manipulations Fig. 3D contained inappropriate data arrangements and manipu- were made in Figs. 1, 2C,S4A,S4B, and 5. To avoid further lations. To avoid further confusion to the related scientific com- confusion to the related scientific community, we hereby retract munity, we hereby retract this report. We sincerely apologize for this report. We sincerely apologize for any inconvenience from any inconvenience from this outcome. All of the authors agreed this outcome. All of the authors agree with the retraction.” with the retraction.” Chihiro Akimoto Kimihiro Yoshimura Takashi Ueda Hirochika Kitagawa Kazuki Inoue Ryoji Fujiki Ikuko Yamaoka Masahiko Tanabe Matomo Sakari Shinichiro Takezawa Wataru Obara Ichiro Takada Tomoaki Fujioka Ikuko Yamaoka Akira Nagahara Masayoshi Yonezawa Norio Nonomura Takeshi Kondo Syuichi Tsutsumi Yoshiyuki Furutani Hiroyuki Aburatani Hisato Yagi Tsuneharu Miki Shin Yoshinaga Takahiro Matsumoto Takeyoshi Masuda Hirochika Kitagawa Toru Fukuda Shigeaki Kato Yoko Yamamoto www.pnas.org/cgi/doi/10.1073/pnas.1323399111 Kanae Ebihara Dean Y. Li Rumiko Matsuoka Jun K. Takeuchi Takahiro Matsumoto Shigeaki Kato www.pnas.org/cgi/doi/10.1073/pnas.1323397111 2398 | www.pnas.org Downloaded by guest on September 29, 2021 Mod5 protein binds to tRNA gene complexes and PNAS PLUS affects local transcriptional silencing Matthew Pratt-Hyatta,b,1, Dave A. Paia, Rebecca A. Haeuslera,2, Glenn G. Wozniaka, Paul D. Gooda, Erin L. Millera, Ian X. McLeodc,3, John R. Yates IIIc, Anita K. Hopperd, and David R. Engelkea,b,4 aDepartment of Biological Chemistry and bCellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109-0606; cDepartment of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; and dDepartment of Molecular Genetics, The Ohio State University, Columbus, OH 43210 Edited* by John Abelson, CalTech, University of California, San Francisco, CA, and approved July 3, 2013 (received for review December 5, 2012) The tRNA gene-mediated (tgm) silencing of RNA polymerase II tRNAPhe, and tRNASer (14–17). In addition, no other tRNA promoters is dependent on subnuclear clustering of the tRNA processing enzymes that we tested were required for the silenc- genes, but genetic analysis shows that the silencing requires ing, and therefore, it did not seem that tRNA maturation per se additional mechanisms. We have identified proteins that bind was needed (3). Here, we show that Mod5 binds to tRNA genes tRNA gene transcription complexes and are required for tgm in vivo and the pre-tRNA transcripts, even if the RNA is not an silencing but not required for gene clustering. One of the proteins, appropriate substrate for Mod5. Possible explanations for the Mod5, is a tRNA modifying enzyme that adds an N6-isopentenyl role of Mod5 and the pre-tRNA transcripts are discussed. adenosine modification at position 37 on a small number of tRNAs in the cytoplasm, although a subpopulation of Mod5 is also found Results in the nucleus. Recent publications have also shown that Mod5 has Mod5 Is Required for Silencing near tRNA Genes. Over 200 gene tumor suppressor characteristics in humans as well as confers drug deletions and mutations have previously been tested to de- resistance through prion-like misfolding in yeast. Here, we show termine which proteins are necessary for tgm silencing (3, 18). that a subpopulation of Mod5 associates with tRNA gene com- The plasmid reporter construct contains an active tRNA gene plexes in the nucleolus. This association occurs and is required for upstream of an HIS3 coding region in strains where the chro- tgm silencing regardless of whether the pre-tRNA transcripts are mosomal HIS3 gene is deleted. HIS3 transcription is controlled BIOCHEMISTRY substrates for Mod5 modification. In addition, Mod5 is bound to by a modified GAL1 promoter with a single, consensus upstream nuclear pre-tRNA transcripts, although they are not substrates for activation sequence (UASG) binding site for Gal4 protein (Fig. the A37 modification. Lastly, we show that truncation of the tRNA 1A). WT cells are not able to grow in the absence of histidine, transcript to remove the normal tRNA structure also alleviates because the tRNA gene prevents pol II transcription (Fig. 1A), silencing, suggesting that synthesis of intact pre-tRNAs is required even when Gal4 is bound to the UASG (2, 18). for the silencing mechanism. These results are discussed in light of Most mutations previously shown to alleviate tgm silencing recent results showing that silencing near tRNA genes also cause a mislocalization of the tRNA genes, and therefore, they requires chromatin modification. no longer cluster near the nucleolus (3). These mutations typi- cally cause poor growth of the mutant yeast strains, because they RNA silencing | Maf1 usually disrupt nucleolar architecture. An exception is the de- letion of MAF1, which both derepresses tRNA gene transcrip- ranscription silencing can occur near yeast tRNA genes, tion and alleviates tgm silencing (9), but it does not have any MAF1 Twhich are distributed throughout the linear chromosomes detectable growth phenotype. Because is known to affect (1, 2). The tendency of tRNA genes to suppress transcription both localization and function of another protein Mod5, a known from nearby RNA polymerase II (pol II) promoters is mechanis- tically distinct from other forms of silencing in yeast, because gene Significance mutations and deletions that affect other silencing mechanisms fail to affect tRNA gene-mediated (tgm) silencing (3). This tgm This study provides new insight into the requirements for ob- silencing is also distinct from the ability of tRNA genes to serve as served silencing of RNA polymerase II transcription near tRNA insulators or boundary elements, because it requires the tRNA genes. Mod5 is a conserved tRNA modification enzyme found gene to be transcribed (2) rather than requiring only the presence in both the nucleus and cytoplasm, although it only modifies of the TFIIIC transcription factor (4–6).This form of silencing tRNAs in the cytoplasm. Mod5 is required for silencing near depends on the subnuclear localization of the tRNA loci to the tRNA genes, and it is bound to both nuclear tRNA gene com- nucleolus and is relieved when nucleolar architecture is compro- plexes and nuclear pre-tRNA transcripts. Possible mecha- mised (3, 7). The correlation between the loss of silencing and the nisms for this form of RNA-mediated transcriptional silencing loss of subnuclear localization raised the question of whether are discussed. nucleolar localization alone was sufficient to suppress nearby pol Author contributions: M.P.-H., A.K.H., and D.R.E.
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