Leishmania mexicana N-Acetyltransferease 10 Is Important for Polysome Formation and Cell Cycle Progression

被引:0
|
作者
Maran, Suellen Rodrigues [1 ,2 ]
Leite, Ariely Barbosa [1 ,2 ]
Alves, Gabriela Gomes [1 ]
Bonifacio, Bruno Souza [1 ,2 ]
Alves, Carlos Eduardo [1 ,2 ]
Moreira, Paulo Otavio Lourenco [3 ]
Panessa, Giovanna Marques [4 ]
Prado, Heloisa Monteiro do Amaral [5 ]
Klippel, Angelica Hollunder [5 ]
Cussiol, Jose Renato [4 ]
Massirer, Katlin Brauer [5 ]
Ferreira, Tiago Rodrigues [6 ]
Sacks, David [6 ]
Barbieri, Clara Lucia [2 ]
da Silva, Marcelo Santos [7 ]
do Monte-Neto, Rubens Lima [3 ]
Moretti, Nilmar Silvio [1 ,2 ,8 ,9 ]
机构
[1] Univ Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Lab Biol Mol Patogenos LBMP, Sao Paulo, Brazil
[2] Univ Fed Sao Paulo UNIFESP, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo, Brazil
[3] Fundacao Oswaldo Cruz, Grp Pesquisas Biotecnol Aplicada Ao Estudo Patogen, Inst Rene Rachou, Belo Horizonte, MG, Brazil
[4] Univ Fed Sao Paulo, Dept Bioquim, Escola Paulista Med, Sao Paulo, Brazil
[5] Univ Estadual Campinas UNICAMP, Ctr Mol Biol & Genet Engn CBMEG, Ctr Med Chem CQMED, Campinas, Brazil
[6] NIAID, Lab Parasit Dis, NIH, Bethesda, MD USA
[7] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, Brazil
[8] Univ Montreal, Fac Vet Med, St Hyacinthe, PQ, Canada
[9] Univ Montreal, Res Grp Infect Dis Prod Anim GREMIP, FMV, St Hyacinthe, PQ, Canada
关键词
ac4C; acetylation; acetyltransferase; differentiation; <italic>Leishmania</italic>; NAT10; GENE-EXPRESSION; DNA-SYNTHESIS; CLONING; NAT10; TRYPANOSOMES; DIAGNOSIS; PROTEIN;
D O I
10.1111/mmi.15338
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs. Recent studies have shown that mRNAs in humans undergo a modification known as N4-acetylcytidine (ac4C) catalyzed by the enzyme N-acetyltransferase (NAT10), impacting mRNAs stability and translation. Here, we characterized the NAT10 homologue of L. mexicana, finding that the enzyme exhibits all the conserved acetyltransferase domains although failed to functionally complement the Kre33 mutant in Saccharomyces cerevisiae. We also discovered that LmexNAT10 is nuclear, and seems essential, as evidenced by unsuccessful attempts to obtain null mutant parasites. Phenotypic characterization of single-knockout parasites revealed that LmexNAT10 affects the multiplication of procyclic forms and the promastigote-amastigote differentiation. Additionally, in vivo infection studies using the invertebrate vector Lutzomyia longipalpis showed a delay in the parasite differentiation into metacyclics. Finally, we observed changes in the cell cycle progression and protein synthesis in the mutant parasites. Together, these results suggest that LmexNAT10 might be important for parasite differentiation, potentially by regulating ac4C levels.
引用
收藏
页码:60 / 74
页数:15
相关论文
共 50 条
  • [1] The CRK3 protein kinase is essential for cell cycle progression of Leishmania Mexicana
    Hassan, P
    Fergusson, D
    Grant, KM
    Mottram, JC
    MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2001, 113 (02) : 189 - 198
  • [2] Whole cell reconstructions of Leishmania mexicana through the cell cycle
    Hair, Molly
    Yanase, Ryuji
    Moreira-Leite, Flavia
    Wheeler, Richard John
    Sadlova, Jovana
    Volf, Petr
    Vaughan, Sue
    Sunter, Jack Daniel
    PLOS PATHOGENS, 2024, 20 (02)
  • [3] Son is Important for Cell Cycle Progression
    Torres-Munoz, K. N.
    Sharma, A.
    Bubulya, P. A.
    MOLECULAR BIOLOGY OF THE CELL, 2011, 22
  • [4] An essential role for the Leishmania major metacaspase in cell cycle progression
    A Ambit
    N Fasel
    G H Coombs
    J C Mottram
    Cell Death & Differentiation, 2008, 15 : 113 - 122
  • [5] An essential role for the Leishmania major metacaspase in cell cycle progression
    Ambit, A.
    Fasel, N.
    Coombs, G. H.
    Mottram, J. C.
    CELL DEATH AND DIFFERENTIATION, 2008, 15 (01): : 113 - 122
  • [6] Identification of the human Nα-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression
    Starheim, Kristian K.
    Arnesen, Thomas
    Gromyko, Darina
    Ryningen, Anita
    Varhaug, Jan Erik
    Lillehaug, Johan R.
    BIOCHEMICAL JOURNAL, 2008, 415 (02) : 325 - 331
  • [7] Kinetoplast Morphology and Segregation Pattern as a Marker for Cell Cycle Progression in Leishmania donovani
    Minocha, Neha
    Kumar, Devanand
    Rajanala, Kalpana
    Saha, Swati
    JOURNAL OF EUKARYOTIC MICROBIOLOGY, 2011, 58 (03) : 249 - 253
  • [8] Analysis of the Leishmania mexicana promastigote cell cycle using imaging flow cytometry provides new insights into cell cycle flexibility and events of short duration
    Howell, Jessie
    Omwenga, Sulochana
    Jimenez, Melanie
    Hammarton, Tansy C.
    PLOS ONE, 2024, 19 (10):
  • [9] Conditional gene deletion with DiCre demonstrates an essential role for CRK3 in Leishmania mexicana cell cycle regulation
    Duncan, Samuel M.
    Myburgh, Elmarie
    Philipon, Cintia
    Brown, Elaine
    Meissner, Markus
    Brewer, James
    Mottram, Jeremy C.
    MOLECULAR MICROBIOLOGY, 2016, 100 (06) : 931 - 944
  • [10] Spindle Matrix Formation is Required for Cell Cycle Progression.
    Johansen, J.
    Yao, C.
    Wang, C.
    Li, Y.
    Girton, J.
    Johansen, K. M.
    MOLECULAR BIOLOGY OF THE CELL, 2014, 25