La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate.
Translation initiation on poliovirus RNA occurs by internal binding of ribosomes to a sequence within the 5' untranslated region. We have previously characterized a HeLa cell protein, p52, that binds to a fragment of the poliovirus 5' untranslated region (K. Meerovitch, J. Pelletier, and N. Sonenberg, Genes Dev. 3:1026-1034, 1989). Here we report the purification of the HeLa p52. Protein microsequencing identified p52 as La autoantigen. The La protein is a human antigen that is recognized by antibodies from patients with autoimmune disorders such as systemic lupus erythematosus and Sjögren's syndrome. We show that the La protein stimulates translation of poliovirus RNA, but not brome mosaic virus, tobacco mosaic virus, and alfalfa mosaic virus 4 RNA, translation in a reticulocyte lysate. In addition, La corrects aberrant translation of poliovirus RNA in a reticulocyte lysate. Subcellular immunolocalization showed that La protein is mainly nuclear, but after poliovirus infection, La is redistributed to the cytoplasm. Our results suggest that La protein is involved in poliovirus internal initiation of translation and might function through a similar mechanism in the translation of cellular mRNAs.
Meerovitch
K
K
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Svitkin
Y V
YV
Lee
H S
HS
Lejbkowicz
F
F
Kenan
D J
DJ
Chan
E K
EK
Agol
V I
VI
Keene
J D
JD
Sonenberg
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D002451:Cell Compartmentation; D002474:Cell-Free System; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011051:Poliomyelitis / Q000378:metabolism / Q000382:microbiology; D017955:Poliovirus / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D011817:Rabbits; D012156:Reticulocytes; D012261:Ribonucleoproteins / Q000502:physiology*; D000097585:SS-B Antigen
D001324:Autoantigens; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen