La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate

Abstract

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 Sjogren'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.

La, PTB, and PAB proteins bind to the 3′ untranslated region of Norwalk virus genomic RNA

“…Besides the finding of PABP bound to the 3 0 UTR(A), two other cellular proteins, La and rPTB, were identified by immunoprecipitation and crosslinking assays, respectively. This is an interesting finding because both proteins are also associated to some viral functions: La has an essential role in PV translation [29] while PTB is necessary for PV and hepatitis C (HCV) translation [16,30] and mouse hepatitis virus RNA synthesis [31].…”

Role of RNA chaperones in virus replication

“…La has RNA chaperone activity, as it facilitates group I intron splicing both in vitro and in vivo (Belisova et al, 2005). La interacts with the UTR regions of HCV and poliovirus, and enhances translation from the IRES of these viruses (Domitrovich et al, 2005;Meerovitch et al, 1993). In addition, La autoantigen is also required for efficient replication of HCV viral RNA (Domitrovich et al, 2005).…”

Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

“…For example, the cellular proteins La, Sam68, nucleolin and polypyrimidine tract binding protein (PTB) have all been shown to interact with poliovirus RNA or proteins (Borman et al, 1993;Hellen et al, 1993;McBride et al, 1996;Meerovitch et al, 1993;Waggoner and Sarnow, 1998). La, Sam68, nucleolin and PTB are predominantly nuclear in uninfected cells, but following infection with poliovirus they accumulate in the cytoplasm (Table 1and Back McBride et al, 1996;Meerovitch et al, 1993;Waggoner and Sarnow, 1998). The accumulation of these proteins in the cytoplasm of cells could be brought about by a variety of mechanisms, however, recent data suggests that poliovirus inhibits the nuclear import of these cellular factors, resulting in their accumulation in the cytoplasm of cells.…”