       Document 0108
 DOCN  M9460108
 TI    Two functional domains of the influenza virus NS1 protein are required
       for regulation of nuclear export of mRNA.
 DT    9404
 AU    Qian XY; Alonso-Caplen F; Krug RM; Department of Molecular Biology and
       Biochemistry, Rutgers; University, Piscataway, New Jersey 08855-1179.
 SO    J Virol. 1994 Apr;68(4):2433-41. Unique Identifier : AIDSLINE
       MED/94187085
 AB    The influenza virus NS1 protein is the only known example of a protein
       that inhibits the nuclear export of mRNA. To identify the functional
       domains of this protein, we introduced 18 2- or 3-amino-acid
       substitutions at approximately equally spaced locations along the entire
       length of the protein. Two functional domains were identified. The
       domain near the amino end (amino acids 19 through 38) was shown to be
       the RNA-binding domain, by using a gel shift assay with purified NS1
       protein and spliced viral NS2 mRNA as the RNA target. The second domain,
       which is in the carboxy half of the molecule, was presumed to be the
       effector domain that interacts with host nuclear proteins to carry out
       the nuclear RNA export function, by analogy with the effector domain of
       the Rev proteins of human immunodeficiency virus (HIV) and other
       lentiviruses which facilitate rather than inhibit nuclear RNA export.
       The NS1 protein has a 10-amino-acid sequence that is similar to the
       consensus sequence in the effector domains of lentivirus Rev proteins,
       specifically including two crucial leucines at positions 7 and 9 of this
       sequence. However, the effector domains of the NS1 and Rev (HIV type 1
       [HIV-1]) proteins differed in several significant ways including the
       following: (i) unlike the HIV-1 Rev protein, NS1 effector domain mutants
       were negative recessive rather than negative dominant, (ii) the NS1
       effector domain is about three times larger than the effector domain of
       the HIV-1 Rev protein, and (iii) unlike the HIV-1 protein, NS1 effector
       domain mutants exhibited a surprising property, a changed
       intracellular/intranuclear distribution, compared with the wild-type
       protein. These differences strongly suggest that the effector domains of
       the NS1 and Rev proteins interact with different nuclear protein
       targets, which likely explains the opposite effects of these two
       proteins on nuclear mRNA export.
 DE    Amino Acid Sequence  Biological Transport  Cell Compartmentation  Cell
       Nucleus/*METABOLISM  Comparative Study  DNA Mutational Analysis  Gene
       Products, rev/GENETICS  Molecular Sequence Data  Mutagenesis,
       Site-Directed  Orthomyxoviridae/GENETICS/*METABOLISM  Protein Binding
       Recombinant Proteins/METABOLISM  RNA-Binding
       Proteins/GENETICS/*METABOLISM  RNA, Messenger/*METABOLISM
       Structure-Activity Relationship  Support, U.S. Gov't, P.H.S.  Viral
       Nonstructural Proteins/GENETICS/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

