دورية أكاديمية
Purine-responsive expression of the Leishmania donovani NT3 purine nucleobase transporter is mediated by a conserved RNA stem-loop.
| العنوان: | Purine-responsive expression of the Leishmania donovani NT3 purine nucleobase transporter is mediated by a conserved RNA stem-loop. |
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| المؤلفون: | Licon MH; Department of Molecular Microbiology, Oregon Health & Science University, Portland, Oregon, USA., Yates PA; Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, Oregon, USA yatesp@ohsu.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2020 Jun 19; Vol. 295 (25), pp. 8449-8459. Date of Electronic Publication: 2020 Apr 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Leishmania donovani/*metabolism , Nucleobase Transport Proteins/*metabolism , Protozoan Proteins/*metabolism , Purines/*metabolism, 3' Untranslated Regions ; Base Sequence ; Culture Media/chemistry ; Genomic Instability ; Leishmania donovani/genetics ; Mutagenesis ; Nucleic Acid Conformation ; Nucleobase Transport Proteins/genetics ; Protozoan Proteins/genetics ; RNA, Messenger/chemistry ; RNA, Messenger/metabolism ; Trypanosoma brucei brucei/metabolism |
| مستخلص: | The ability to modulate gene expression in response to changes in the host environment is essential for survival of the kinetoplastid parasite Leishmania Unlike most eukaryotes, gene expression in kinetoplastids is predominately regulated posttranscriptionally. Consequently, RNA-binding proteins and mRNA-encoded sequence elements serve as primary determinants of gene regulation in these organisms; however, few have defined roles in specific stress response pathways. Leishmania species cannot synthesize purines de novo and must scavenge these essential nutrients from the host. Leishmania have evolved a robust stress response to withstand sustained periods of purine scarcity during their life cycle. The purine nucleobase transporter LdNT3 is among the most substantially up-regulated proteins in purine-starved Leishmania donovani parasites. Here we report that the posttranslational stability of the LdNT3 protein is unchanged in response to purine starvation. Instead, LdNT3 up-regulation is primarily mediated by a 33-nucleotide-long sequence in the LdNT3 mRNA 3' UTR that is predicted to adopt a stem-loop structure. Although this sequence is highly conserved within the mRNAs of orthologous transporters in multiple kinetoplastid species, putative stem-loops from L. donovani and Trypanosoma brucei nucleobase transporter mRNAs were not functionally interchangeable for purine-responsive regulation. Through mutational analysis of the element, we demonstrate that species specificity is attributable to just three variant bases within the predicted loop. Finally, we provide evidence that the abundance of the trans- acting factor that binds the LdNT3 stem-loop in vivo is substantially higher than required for regulation of LdNT3 alone, implying a potential role in regulating other purine-responsive genes. Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article. (© 2020 Licon and Yates.) |
| References: | Nat Biotechnol. 2004 May;22(5):589-94. (PMID: 15064769) Cell Microbiol. 2017 Oct;19(10):. (PMID: 28580630) Mol Biochem Parasitol. 2011 Feb;175(2):209-12. (PMID: 21055426) Open Biol. 2019 Jun 28;9(6):190072. (PMID: 31164043) Mol Biochem Parasitol. 2003 May;128(2):217-28. (PMID: 12742588) Trends Biotechnol. 2006 Feb;24(2):68-75. (PMID: 16380176) Mol Biol Cell. 2011 Nov;22(22):4205-19. (PMID: 21965287) Exp Parasitol. 1993 Jun;76(4):412-23. (PMID: 8513879) PLoS Pathog. 2014 Feb 27;10(2):e1003938. (PMID: 24586154) Mol Biochem Parasitol. 2003 Aug 11;130(1):31-42. (PMID: 14550894) J Eukaryot Microbiol. 2016 Sep;63(5):657-78. (PMID: 27009761) PLoS Negl Trop Dis. 2012;6(9):e1833. (PMID: 23050028) Mol Biochem Parasitol. 2015 Dec;204(2):89-92. (PMID: 26844641) Acta Trop. 2002 Jul;83(1):37-42. (PMID: 12062791) Science. 2005 Jul 15;309(5733):436-42. (PMID: 16020728) Nucleic Acids Res. 2015 Aug 18;43(14):6799-813. (PMID: 26150419) World Health Organ Tech Rep Ser. 2010;(949):xii-xiii, 1-186, back cover. (PMID: 21485694) Genome Res. 2020 Jul;30(7):962-973. (PMID: 32703884) Trends Parasitol. 2012 Aug;28(8):345-52. (PMID: 22726696) PLoS Pathog. 2013;9(4):e1003286. (PMID: 23592996) FASEB J. 2008 Feb;22(2):590-602. (PMID: 17884972) Int J Parasitol. 2004 Feb;34(2):205-17. (PMID: 15037106) Mol Biochem Parasitol. 2014 Jun;195(1):1-5. (PMID: 24878002) Nucleic Acids Res. 2003 Jul 1;31(13):3406-15. (PMID: 12824337) Nucleic Acids Res. 2014 Jun;42(11):7201-9. (PMID: 24813448) Mol Microbiol. 2016 Jul;101(2):299-313. (PMID: 27062185) Mol Microbiol. 2010 Oct;78(1):92-107. (PMID: 20923417) Mol Cell. 2018 Jun 7;70(5):854-867.e9. (PMID: 29883606) Nucleic Acids Res. 2011 Jul;39(Web Server issue):W13-7. (PMID: 21558174) |
| معلومات مُعتمدة: | R03 AI137636 United States AI NIAID NIH HHS; T32 AI007472 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Leishmania; adaptation; mRNA; parasitology; posttranscriptional regulation; purine; starvation; stress response; transporter |
| المشرفين على المادة: | 0 (3' Untranslated Regions) 0 (Culture Media) 0 (Nucleobase Transport Proteins) 0 (Protozoan Proteins) 0 (Purines) 0 (RNA, Messenger) |
| تواريخ الأحداث: | Date Created: 20200502 Date Completed: 20210105 Latest Revision: 20240329 |
| رمز التحديث: | 20240329 |
| مُعرف محوري في PubMed: | PMC7307198 |
| DOI: | 10.1074/jbc.RA120.012696 |
| PMID: | 32354744 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
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| DOI: | 10.1074/jbc.RA120.012696 |