دورية أكاديمية
أعرض في EDS

N 6 -methyladenosine in poly(A) tails stabilize VSG transcripts.

التفاصيل البيبلوغرافية
العنوان: N 6 -methyladenosine in poly(A) tails stabilize VSG transcripts.
المؤلفون: Viegas IJ; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., de Macedo JP; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Serra L; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., De Niz M; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Temporão A; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Silva Pereira S; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Mirza AH; Department of Pharmacology, Weill Medical College, Cornell University, New York, NY, USA., Bergstrom E; Department of Chemistry, University of York, York, UK.; Centre of Excellence in Mass Spectrometry, University of York, York, UK., Rodrigues JA; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Clarify Analytical, Évora, Portugal., Aresta-Branco F; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Division of Immune Diversity, German Cancer Research Center, Heidelberg, Germany.; Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany., Jaffrey SR; Department of Pharmacology, Weill Medical College, Cornell University, New York, NY, USA., Figueiredo LM; Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. lmf@medicina.ulisboa.pt.
المصدر: Nature [Nature] 2022 Apr; Vol. 604 (7905), pp. 362-370. Date of Electronic Publication: 2022 Mar 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: RNA Processing, Post-Transcriptional* , Trypanosoma brucei brucei*/genetics , Variant Surface Glycoproteins, Trypanosoma*/genetics, 3' Untranslated Regions/genetics ; Adenosine/analogs & derivatives ; Gene Expression Regulation ; RNA/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcription, Genetic
مستخلص: RNA modifications are important regulators of gene expression 1 . In Trypanosoma brucei, transcription is polycistronic and thus most regulation happens post-transcriptionally 2 . N 6 -methyladenosine (m 6 A) has been detected in this parasite, but its function remains unknown 3 . Here we found that m 6 A is enriched in 342 transcripts using RNA immunoprecipitation, with an enrichment in transcripts encoding variant surface glycoproteins (VSGs). Approximately 50% of the m 6 A is located in the poly(A) tail of the actively expressed VSG transcripts. m 6 A residues are removed from the VSG poly(A) tail before deadenylation and mRNA degradation. Computational analysis revealed an association between m 6 A in the poly(A) tail and a 16-mer motif in the 3' untranslated region of VSG genes. Using genetic tools, we show that the 16-mer motif acts as a cis-acting motif that is required for inclusion of m 6 A in the poly(A) tail. Removal of this motif from the 3' untranslated region of VSG genes results in poly(A) tails lacking m 6 A, rapid deadenylation and mRNA degradation. To our knowledge, this is the first identification of an RNA modification in the poly(A) tail of any eukaryote, uncovering a post-transcriptional mechanism of gene regulation.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
التعليقات: Comment in: Mol Cell. 2022 Jun 2;82(11):1979-1980. (PMID: 35659324)
References: Zaccara, S., Ries, R. J. & Jaffrey, S. R. Reading, writing and erasing mRNA methylation. Nat. Rev. Mol. Cell Biol. 20, 608–624 (2019). (PMID: 10.1038/s41580-019-0168-531520073)
Horn, D. Antigenic variation in African trypanosomes. Mol. Biochem. Parasitol. 195, 123–129 (2014). (PMID: 10.1016/j.molbiopara.2014.05.001248592774155160)
Liu, L. et al. Differential m 6 A methylomes between two major life stages allows potential regulations in Trypanosoma brucei. Biochem. Biophys. Res. Commun. 508, 1286–1290 (2019). (PMID: 10.1016/j.bbrc.2018.12.04330573362)
Franco, J. R., Simarro, P. P., Diarra, A., Ruiz-Postigo, J. A. & Jannin, J. G. The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy. Parasitology 141, 748–760 (2014). (PMID: 10.1017/S003118201300210224709291)
Cross, G. A., Kim, H. S. & Wickstead, B. Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427. Mol. Biochem. Parasitol. 195, 59–73 (2014). (PMID: 10.1016/j.molbiopara.2014.06.00424992042)
Cross, G. A. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71, 393–417 (1975). (PMID: 10.1017/S003118200004717X645)
Nilsson, D. et al. Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei. PLoS Pathog. 6, e1001037 (2010). (PMID: 10.1371/journal.ppat.1001037207004442916883)
Kraus, A. J., Brink, B. G. & Siegel, T. N. Efficient and specific oligo-based depletion of rRNA. Sci Rep. 9, 12281 (2019). (PMID: 10.1038/s41598-019-48692-2314398806706579)
Gunzl, A. et al. RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei. Eukaryot. Cell 2, 542–551 (2003). (PMID: 10.1128/EC.2.3.542-551.200312796299161450)
Fadda, A. et al. Transcriptome-wide analysis of trypanosome mRNA decay reveals complex degradation kinetics and suggests a role for co-transcriptional degradation in determining mRNA levels. Mol. Microbiol. 94, 307–326 (2014). (PMID: 10.1111/mmi.12764251454654285177)
Berberof, M. et al. The 3′-terminal region of the mRNAs for VSG and procyclin can confer stage specificity to gene expression in Trypanosoma brucei. EMBO J. 14, 2925–2934 (1995). (PMID: 10.1002/j.1460-2075.1995.tb07292.x7796818398412)
Ridewood, S. et al. The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei. Mol. Microbiol. 106, 614–634 (2017). (PMID: 10.1111/mmi.13838289060555698767)
Roditi, I. et al. Procyclin gene expression and loss of the variant surface glycoprotein during differentiation of Trypanosoma brucei. J. Cell Biol. 108, 737–746 (1989). (PMID: 10.1083/jcb.108.2.7372645304)
Ehlers, B., Czichos, J. & Overath, P. RNA turnover in Trypanosoma brucei. Mol. Cell. Biol. 7, 1242–1249 (1987). (PMID: 2436040365198)
Matthews, K. R. The developmental cell biology of Trypanosoma brucei. J. Cell Sci. 118, 283–290 (2005). (PMID: 10.1242/jcs.0164915654017)
Wei, C. M., Gershowitz, A. & Moss, B. Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell 4, 379–386 (1975). (PMID: 10.1016/0092-8674(75)90158-0164293)
Perry, R. P., Kelley, D. E., Friderici, K. & Rottman, F. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell 4, 387–394 (1975). (PMID: 10.1016/0092-8674(75)90159-21168101)
Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635–1646 (2012). (PMID: 10.1016/j.cell.2012.05.003226080853383396)
Dominissini, D. et al. Topology of the human and mouse m 6 A RNA methylomes revealed by m 6 A-seq. Nature 485, 201–206 (2012). (PMID: 10.1038/nature1111222575960)
Jia, G. et al. N 6 -methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885–887 (2011). (PMID: 10.1038/nchembio.687220027203218240)
Zheng, G. et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18–29 (2013). (PMID: 10.1016/j.molcel.2012.10.01523177736)
Freistadt, M. S., Cross, G. A. & Robertson, H. D. Discontinuously synthesized mRNA from Trypanosoma brucei contains the highly methylated 5′ cap structure, m 7 GpppA*A*C(2′-O)mU*A. J. Biol. Chem. 263, 15071–15075 (1988). (PMID: 10.1016/S0021-9258(18)68147-52844798)
Bangs, J. D., Crain, P. F., Hashizume, T., McCloskey, J. A. & Boothroyd, J. C. Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel nucleosides. J. Biol. Chem. 267, 9805–9815 (1992). (PMID: 10.1016/S0021-9258(19)50165-X1349605)
Perry, K. L., Watkins, K. P. & Agabian, N. Trypanosome mRNAs have unusual “cap 4” structures acquired by addition of a spliced leader. Proc. Natl Acad. Sci. USA 84, 8190–8194 (1987). (PMID: 10.1073/pnas.84.23.81903120186299507)
Hauenschild, R. et al. The reverse transcription signature of N-1-methyladenosine in RNA-seq is sequence dependent. Nucleic Acids Res. 43, 9950–9964 (2015). (PMID: 263652424787781)
Boccaletto, P. et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 46, D303–D307 (2018). (PMID: 10.1093/nar/gkx103029106616)
Molinie, B. et al. m 6 A-LAIC-seq reveals the census and complexity of the m 6 A epitranscriptome. Nat. Methods 13, 692–698 (2016). (PMID: 10.1038/nmeth.3898273767695704921)
Xiang, J. F. et al. N 6 -methyladenosines modulate A-to-I RNA editing. Mol. Cell 69, 126–135.e6 (2018). (PMID: 10.1016/j.molcel.2017.12.00629304330)
Clayton, C. E. Regulation of gene expression in trypanosomatids: living with polycistronic transcription. Open Biol. 9, 190072 (2019). (PMID: 10.1098/rsob.190072311640436597758)
Schibler, U., Kelley, D. E. & Perry, R. P. Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J. Mol. Biol. 115, 695–714 (1977). (PMID: 10.1016/0022-2836(77)90110-3592376)
Linder, B. et al. Single-nucleotide-resolution mapping of m 6 A and m 6 Am throughout the transcriptome. Nat. Methods 12, 767–772 (2015). (PMID: 10.1038/nmeth.3453261214034487409)
Hoek, M., Zanders, T. & Cross, G. A. M. Trypanosoma brucei expression-site-associated-gene 8 protein interacts with a Pumilio family protein. Mol. Biochem. Parasitol. 120, 269–283 (2002). (PMID: 10.1016/S0166-6851(02)00009-911897132)
Iyer, L. M., Zhang, D. & Aravind, L. Adenine methylation in eukaryotes: apprehending the complex evolutionary history and functional potential of an epigenetic modification. Bioessays 38, 27–40 (2016). (PMID: 10.1002/bies.20150010426660621)
Domingo-Sananes, M. R., Szoor, B., Ferguson, M. A., Urbaniak, M. D. & Matthews, K. R. Molecular control of irreversible bistability during trypanosome developmental commitment. J. Cell Biol. 211, 455–468 (2015). (PMID: 10.1083/jcb.201506114264835584621835)
Melo do Nascimento, L. et al. Functional insights from a surface antigen mRNA-bound proteome. eLife 10, e68136 (2021). (PMID: 10.7554/eLife.68136337833588051951)
Fadda, A., Färber, V., Droll, D. & Clayton, C. The roles of 3′-exoribonucleases and the exosome in trypanosome mRNA degradation. RNA 19, 937–947 (2013). (PMID: 10.1261/rna.038430.113236975493683928)
Schwede, A. et al. A role for Caf1 in mRNA deadenylation and decay in trypanosomes and human cells. Nucleic Acids Res. 36, 3374–3388 (2008). (PMID: 10.1093/nar/gkn108184429962425496)
Gallie, D. R. The role of the poly(A) binding protein in the assembly of the Cap-binding complex during translation initiation in plants. Translation (Austin) 2, e959378 (2014).
Garneau, N. L., Wilusz, J. & Wilusz, C. J. The highways and byways of mRNA decay. Nat. Rev. Mol. Cell Biol. 8, 113–126 (2007). (PMID: 10.1038/nrm210417245413)
Chen, C. Y. & Shyu, A. B. Mechanisms of deadenylation-dependent decay. Wiley Interdiscip. Rev. RNA 2, 167–183 (2011). (PMID: 10.1002/wrna.4021957004)
Decker, C. J. & Parker, R. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation. Genes Dev. 7, 1632–1643 (1993). (PMID: 10.1101/gad.7.8.16328393418)
Tang, T. T. L., Stowell, J. A. W., Hill, C. H. & Passmore, L. A. The intrinsic structure of poly(A) RNA determines the specificity of Pan2 and Caf1 deadenylases. Nat. Struct. Mol. Biol. 26, 433–442 (2019). (PMID: 10.1038/s41594-019-0227-9311102946555765)
معلومات مُعتمدة: R35 NS111631 United States NS NINDS NIH HHS; T32 CA062948 United States CA NCI NIH HHS
المشرفين على المادة: 0 (3' Untranslated Regions)
0 (RNA, Messenger)
0 (Variant Surface Glycoproteins, Trypanosoma)
63231-63-0 (RNA)
CLE6G00625 (N-methyladenosine)
K72T3FS567 (Adenosine)
تواريخ الأحداث: Date Created: 20220331 Date Completed: 20220415 Latest Revision: 20221021
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9150445
DOI: 10.1038/s41586-022-04544-0
PMID: 35355019
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-022-04544-0