The influenza virus NS1 protein is an RNA-binding protein with multiple functions

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" The influenza virus NS1 protein is an RNA-binding protein with multiple functions "
W. Wang R. M. Krug

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	1113481
Doc. No	:	TLpq304451729
Main Entry	:	R. M. Krug
	:	W. Wang
Title & Author	:	The influenza virus NS1 protein is an RNA-binding protein with multiple functions\ W. WangR. M. Krug
College	:	Rutgers The State University of New Jersey - New Brunswick
Date	:	1998
student score	:	1998
Degree	:	Ph.D.
Page No	:	126
Abstract	:	The influenza virus NS1 protein is an RNA-binding protein with multiple functions. The NS1 protein of the influenza A/Udorn/72 virus possesses two functional domains: an RNA-binding/dimerization domain composed of the first 73 amino acids and an effector domain in the carboxyl-half of the molecule. The NS1A protein inhibits the splicing of the major class of mammalian pre-mRNAs (GU-AG introns) by binding to a specific stem-bulge in U6 snRNA, thereby blocking the formation of U4/U6 and U2/U6 complexes. The splicing of the minor class of AT-AC introns takes place on spliceosomes that do not contain U6 snRNA. Nonetheless, I demonstrate that the NS1 protein inhibits AT-AC splicing in vitro, and specifically binds to only U6atac snRNA--a highly divergent U6 snRNA counterpart, among the five minor class snRNAs. I also show that the NS1 protein inhibits the formation of U12/U6atac complexes, but not the formation of U4atac/U6atac complexes. Though the NS1 proteins of influenza A and B viruses share little sequence homology, an RNA-binding/dimerization domain with the same activities is preserved in the NS1 protein of influenza B/Lee/40 virus. In contrast, the NS1B protein does not contain a functional effector domain like that of the NS1A protein. In addition, a naturally-occurring, truncated viral NS1A protein (A/Turkey/Oregon/71) also lacks such an effector domain. I propose that the essential role of NS1 protein in virus-infected cells is to block the activation of PKR kinase by sequestering double-stranded RNA. The RNA-binding/dimerization domain of NS1A protein exhibits a novel dimeric six-helical chain fold that differs from that of any other RNA-binding protein. I have mapped the RNA-binding site to the Arg/Lys-rich helix 2 region. Helix 2 and helix 2 are anti-parallel and next to each other in the dimeric conformation. My results indicate that these two helices constitute the interaction face between the NS1 protein and its RNA targets. My results also indicate that the NS1 protein can only bind to RNA as a dimer and that the same interaction face is used for different RNA targets.
Subject	:	Biological sciences
	:	Influenza virus
	:	Microbiology
	:	Molecular biology
	:	NS1 protein
	:	RNA-binding protein