Keywords
Last Name

Inna Afasizheva, PhD

TitleAssistant Professor
InstitutionBoston University Henry M. Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology
Phone(617) 414-1049
ORCID ORCID Icon0000-0003-2695-2950
 Research Expertise & Professional Interests
molecular biology
mitochondrial gene expression
RNA editing

Regulation of Mitochondrial Gene Expression by Pentatricopeptide Repeat RNA Binding Proteins -
The majority of trypanosomal mitochondrial pre-mRNAs undergo massive uridine insertion/deletion editing which creates open reading frames. However, our recent findings indicated that pre- and post-editing processing steps are also required to produce translation-competent mRNAs. Pre-editing addition of short 3' A-tails exerts no influence on unedited pre-mRNA stability, but stabilizes transcripts that are edited beyond few initial sites. The post-editing extension of A-tails into A/U heteropolymers by KPAP1 poly(A) polymerase and RET1 TUTase commits fully-edited mRNAs to translation. To identify factors responsible for coupling of editing, polyadenylation, and translation, we built a comprehensive protein interactions network of respective machineries. The ensuing RNAi screen distinguished several pentatricopeptide repeat-containing (PPR) RNA binding proteins acting to: 1) stabilize mRNA prior to polyadenylation 2) block premature mRNA uridylation and 3) induce transcript-specific adenylation uridylation.

 NIH RePORTER Grants
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Aphasizheva I, Zhang L, Aphasizhev R. Investigating RNA editing factors from trypanosome mitochondria. Methods. 2016 Sep 01; 107:23-33. PMID: 27020893.
    View in: PubMed
  2. Aphasizheva I, Aphasizhev R. U-Insertion/Deletion mRNA-Editing Holoenzyme: Definition in Sight. Trends Parasitol. 2016 Feb; 32(2):144-56. PMID: 26572691.
    View in: PubMed
  3. Aphasizheva I, Zhang L, Wang X, Kaake RM, Huang L, Monti S, Aphasizhev R. RNA binding and core complexes constitute the U-insertion/deletion editosome. Mol Cell Biol. 2014 Dec 1; 34(23):4329-42. PMID: 25225332.
    View in: PubMed
  4. Aphasizhev R, Aphasizheva I. Mitochondrial RNA editing in trypanosomes: small RNAs in control. Biochimie. 2014 May; 100:125-31. PMID: 24440637.
    View in: PubMed
  5. Aphasizheva I, Maslov DA, Aphasizhev R. Kinetoplast DNA-encoded ribosomal protein S12: a possible functional link between mitochondrial RNA editing and translation in Trypanosoma brucei. RNA Biol. 2013 Nov; 10(11):1679-88. PMID: 24270388.
    View in: PubMed
  6. Aphasizhev R, Aphasizheva I. Emerging roles of PPR proteins in trypanosomes: switches, blocks, and triggers. RNA Biol. 2013; 10(9):1495-500. PMID: 24055869.
    View in: PubMed
  7. Aphasizhev R, Aphasizheva I. Mitochondrial RNA processing in trypanosomes. Res Microbiol. 2011 Sep; 162(7):655-63. PMID: 21596134.
    View in: PubMed
  8. Aphasizheva I, Maslov D, Wang X, Huang L, Aphasizhev R. Pentatricopeptide repeat proteins stimulate mRNA adenylation/uridylation to activate mitochondrial translation in trypanosomes. Mol Cell. 2011 Apr 8; 42(1):106-17. PMID: 21474072.
    View in: PubMed
  9. Aphasizhev R, Aphasizheva I. Uridine insertion/deletion editing in trypanosomes: a playground for RNA-guided information transfer. Wiley Interdiscip Rev RNA. 2011 Sep-Oct; 2(5):669-85. PMID: 21823228.
    View in: PubMed
  10. Stagno J, Aphasizheva I, Bruystens J, Luecke H, Aphasizhev R. Structure of the mitochondrial editosome-like complex associated TUTase 1 reveals divergent mechanisms of UTP selection and domain organization. J Mol Biol. 2010 Jun 11; 399(3):464-75. PMID: 20403364.
    View in: PubMed
  11. Ringpis GE, Aphasizheva I, Wang X, Huang L, Lathrop RH, Hatfield GW, Aphasizhev R. Mechanism of U insertion RNA editing in trypanosome mitochondria: the bimodal TUTase activity of the core complex. J Mol Biol. 2010 Jun 25; 399(5):680-95. PMID: 20362585.
    View in: PubMed
  12. Aphasizheva I, Aphasizhev R. RET1-catalyzed uridylylation shapes the mitochondrial transcriptome in Trypanosoma brucei. Mol Cell Biol. 2010 Mar; 30(6):1555-67. PMID: 20086102.
    View in: PubMed
  13. Aphasizheva I, Ringpis GE, Weng J, Gershon PD, Lathrop RH, Aphasizhev R. Novel TUTase associates with an editosome-like complex in mitochondria of Trypanosoma brucei. RNA. 2009 Jul; 15(7):1322-37. PMID: 19465686.
    View in: PubMed
  14. Weng J, Aphasizheva I, Etheridge RD, Huang L, Wang X, Falick AM, Aphasizhev R. Guide RNA-binding complex from mitochondria of trypanosomatids. Mol Cell. 2008 Oct 24; 32(2):198-209. PMID: 18951088.
    View in: PubMed
  15. Etheridge RD, Aphasizheva I, Gershon PD, Aphasizhev R. 3' adenylation determines mRNA abundance and monitors completion of RNA editing in T. brucei mitochondria. EMBO J. 2008 Jun 4; 27(11):1596-608. PMID: 18464794.
    View in: PubMed
  16. Aphasizhev R, Aphasizheva I. Terminal RNA uridylyltransferases of trypanosomes. Biochim Biophys Acta. 2008 Apr; 1779(4):270-80. PMID: 18191648.
    View in: PubMed
  17. Stagno J, Aphasizheva I, Aphasizhev R, Luecke H. Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases. Proc Natl Acad Sci U S A. 2007 Sep 11; 104(37):14634-9. PMID: 17785418.
    View in: PubMed
  18. Aphasizhev R, Aphasizheva I. RNA editing uridylyltransferases of trypanosomatids. Methods Enzymol. 2007; 424:55-73. PMID: 17662836.
    View in: PubMed
  19. Stagno J, Aphasizheva I, Rosengarth A, Luecke H, Aphasizhev R. UTP-bound and Apo structures of a minimal RNA uridylyltransferase. J Mol Biol. 2007 Feb 23; 366(3):882-99. PMID: 17189640.
    View in: PubMed
  20. Aphasizhev R, Aphasizheva I, Simpson L. Multiple terminal uridylyltransferases of trypanosomes. FEBS Lett. 2004 Aug 13; 572(1-3):15-8. PMID: 15304317.
    View in: PubMed
  21. Nelson RE, Aphasizheva I, Falick AM, Nebohacova M, Simpson L. The I-complex in Leishmania tarentolae is an uniquely-structured F(1)-ATPase. Mol Biochem Parasitol. 2004 Jun; 135(2):221-4. PMID: 15110463.
    View in: PubMed
  22. Aphasizheva I, Aphasizhev R, Simpson L. RNA-editing terminal uridylyl transferase 1: identification of functional domains by mutational analysis. J Biol Chem. 2004 Jun 4; 279(23):24123-30. PMID: 15060068.
    View in: PubMed
  23. Aphasizhev R, Aphasizheva I, Nelson RE, Gao G, Simpson AM, Kang X, Falick AM, Sbicego S, Simpson L. Isolation of a U-insertion/deletion editing complex from Leishmania tarentolae mitochondria. EMBO J. 2003 Feb 17; 22(4):913-24. PMID: 12574127.
    View in: PubMed
  24. Aphasizhev R, Aphasizheva I, Nelson RE, Simpson L. A 100-kD complex of two RNA-binding proteins from mitochondria of Leishmania tarentolae catalyzes RNA annealing and interacts with several RNA editing components. RNA. 2003 Jan; 9(1):62-76. PMID: 12554877.
    View in: PubMed
  25. Afasizheva IIu, Dolgikh DA, Kirpichnikov MP. [Immunogenic properties of albeferon--biologically active artificial protein]. Mol Biol (Mosk). 1999 Jul-Aug; 33(4):679-83. PMID: 10546223.
    View in: PubMed
  26. Afasizheva IIu, Dolgikh DA, Abdullaev ZKh, Latypov RF, Tiktopulo EI, Uverskii VN, Ptitsyn OB, Kirpichnikov MP. [Effect of a biologically active interferon fragment on the structure of the synthetic protein carrier]. Biofizika. 1998 May-Jun; 43(3):384-91. PMID: 9702328.
    View in: PubMed
  27. Aphasizheva IY, Dolgikh DA, Abdullaev ZK, Uversky VN, Kirpichnikov MP, Ptitsyn OB. Can grafting of an octapeptide improve the structure of a de novo protein? FEBS Lett. 1998 Mar 20; 425(1):101-4. PMID: 9541015.
    View in: PubMed
  28. Latypov RF, Abdullaev ZKh, Badretdinov AIa, Bocharov EV, Mel'nik TN, Afasizheva IIu, Arsen'ev AS, Dolgikh DA, Uverskii VN, Finkel'shtein AV, et al. [Circular permutation of Thermus thermophilus ribosomal protein S6 to artificial protein albebetin topology]. Mol Biol (Mosk). 1998 Jan-Feb; 32(1):125-32. PMID: 9566259.
    View in: PubMed
  29. Aphasizheva IY, Dolgikh DA, Navolotskaya EV, Abramov VM, Zav'yalov VP, Kirpichnikov MP. Biological Activity of de novo Proteins with Incorporated Interferon Fragment. Russ J Immunol. 1997 Apr; 2(1):59-61. PMID: 12687057.
    View in: PubMed
Inna's Networks
Click the "See All" links for more information and interactive visualizations!
Concepts
_
BU Co-Authors
_
Similar BU People
_
Same Department