Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor-specific tRNase

被引:72
作者
Cruz, Jonathan W. [1 ]
Sharp, Jared D. [2 ,3 ]
Hoffer, Eric D. [4 ]
Maehigashi, Tatsuya [4 ]
Vvedenskaya, Irina O. [5 ,6 ]
Konkimalla, Arvind [1 ]
Husson, Robert N. [2 ,3 ]
Nickels, Bryce E. [5 ,6 ,7 ]
Dunham, Christine M. [4 ]
Woychik, Nancy A. [1 ,7 ]
机构
[1] Rutgers Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA
[2] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Emory Univ, Dept Biochem, Sch Med, Atlanta, GA 30322 USA
[5] Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA
[6] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA
[7] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
23S RIBOSOMAL-RNA; ESCHERICHIA-COLI; ANTITOXIN SYSTEMS; CYTOTOXIC RIBONUCLEASE; INHIBITS TRANSLATION; STRUCTURE PREDICTION; PROTEIN EXPRESSION; CRYSTAL-STRUCTURE; CELL-DEATH; CLEAVAGE;
D O I
10.1038/ncomms8480
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Toxin-antitoxin (TA) systems are implicated in the downregulation of bacterial cell growth associated with stress survival and latent tuberculosis infection, yet the activities and intracellular targets of these TA toxins are largely uncharacterized. Here, we use a specialized RNA-seq approach to identify targets of a Mycobacterium tuberculosis VapC TA toxin, VapC-mt4 (also known as VapC4), which have eluded detection using conventional approaches. Distinct from the one other characterized VapC toxin in M. tuberculosis that cuts 23S rRNA at the sarcin-ricin loop, VapC-mt4 selectively targets three of the 45 M. tuberculosis tRNAs (tRNA(Ala2), tRNA(Ser26) and tRNA(Ser24)) for cleavage at, or adjacent to, their anticodons, resulting in the generation of tRNA halves. While tRNA cleavage is sometimes enlisted as a bacterial host defense mechanism, VapC-mt4 instead alters specific tRNAs to inhibit translation and modulate growth. This stress-linked activity of VapC-mt4 mirrors basic features of eukaryotic tRNases that also generate tRNA halves and inhibit translation in response to stress.
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页数:12
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