The hantaviral zoonotic diseases pose a significant threat to human health due to the lack of potential antiviral therapeutics or a vaccine against hantaviruses. N (Sin Nombre hantavirus nucleocapsid protein) augments mRNA translation. N binds to both the mRNA 5′ cap and 40S ribosomal subunit via RPS19 (ribosomal protein S19). N with the assistance of the viral mRNA 5′-UTR preferentially favours the translation of a downstream ORF. We identified and characterized the RPS19-binding domain at the N-terminus of N. Its deletion did not influence the secondary structure, but affected the conformation of trimeric N molecules. The N variant lacking the RPS19-binding region was able to bind both the mRNA 5′ cap and panhandle-like structure, formed by the termini of viral genomic RNA. In addition, the N variant formed stable trimers similar to wild-type N. Use of this variant in multiple experiments provided insights into the mechanism of ribosome loading during N-mediated translation strategy. The present study suggests that N molecules individually associated with the mRNA 5′ cap and RPS19 of the 40S ribosomal subunit undergo N–N interaction to facilitate the engagement of N-associated ribosomes at the mRNA 5′ cap. This has revealed new targets for therapeutic intervention of hantavirus infection.
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November 2014
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Research Article|
October 23 2014
Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism
Safder S. Ganaie;
Safder S. Ganaie
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
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Absarul Haque;
Absarul Haque
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
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Erdong Cheng;
Erdong Cheng
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
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Tania S. Bonny;
Tania S. Bonny
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
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Nilshad N. Salim;
Nilshad N. Salim
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
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Mohammad A. Mir
Mohammad A. Mir
1
*Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, U.S.A.
1To whom correspondence should be addressed (email mmir@kumc.edu).
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Biochem J (2014) 464 (1): 109–121.
Article history
Received:
April 17 2014
Revision Received:
July 07 2014
Accepted:
July 25 2014
Accepted Manuscript online:
July 25 2014
Citation
Safder S. Ganaie, Absarul Haque, Erdong Cheng, Tania S. Bonny, Nilshad N. Salim, Mohammad A. Mir; Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism. Biochem J 15 November 2014; 464 (1): 109–121. doi: https://doi.org/10.1042/BJ20140449
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