Cytoplasmic RNA modulators of an inside-out signal-transduction cascade.
A vaccinia virus-based RNA expression system enabled high-level cytoplasmic expression of RNA aptamers directed against the intracellular domain of the beta2 integrin LFA-1, a transmembrane protein that mediates cell adhesion to intercellular adhesion molecule-1 (ICAM-1). In two different cell types, cytoplasmic expression of integrin-binding aptamers reduced inducible cell adhesion to ICAM-1. The aptamers specifically target, and thereby define, a functional cytoplasmic subdomain important for the regulation of cell adhesion in leukocytes. Our approach of aptamer-controlled blocking of signaling pathways in vivo could potentially be applied wherever targeted modulation of a signal-transduction cascade is desired.
Blind
M
M
Institut für Biochemie, Ludwig-Maximilians-Universität Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Kolanus
W
W
Famulok
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D003593:Cytoplasm / Q000502:physiology; D017931:DNA Primers; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics*
D017931:DNA Primers; D016169:Lymphocyte Function-Associated Antigen-1; D012367:RNA, Viral; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1