Human ribosomal protein L18a interacts with hepatitis C virus internal ribosome entry site

Abstract

Translation initiation of hepatitis C virus RNA occurs via ribosome binding to an 'internal ribosome entry site (IRES)' located in the 5'untranslated region of the viral RNA. The principle interaction between the 40S ribosomal subunit and the HCV IRES has been shown to be largely factor independent, which is followed by the joining of the 60S ribosomal subunit to form functional 80S complex. However several additional cellular proteins have been reported to bind to HCV IRES and enhance the initiation of translation. In order to identify novel factors involved in the ribosome assembly during internal initiation of HCV RNA, northwestern screening of a HeLa cDNA expression library was performed, using HCV IRES RNA as probe. We demonstrate here, that human ribosomal protein L18a, a constituent of 60S subunit, interacts with HCV IRES RNA. This interaction was further confirmed by using a recombinant protein similar to L18a (sL18a), cloned from human blood. Interestingly, addition of increasing concentration of the purified recombinant sL18a protein, showed moderate stimulation of HCV IRES activity in the in vitro translation assay. These observations suggest that the human L18a might influence the HCV IRES mediated translation.

Human T-cell Leukemia Virus Type I p30 Nuclear/Nucleolar Retention Is Mediated through Interactions with RNA and a Constituent of the 60 S Ribosomal Subunit

“…Consistent with its role in RNA trafficking, p30 nuclear/nucleolar retention is partially dependent on de novo mRNA transcription. We also report that p30 interacts with a nucleolar constituent of the large ribosomal subunit L18a, a protein shown previously (12,(32)(33)(34) to modulate internal initiation of translation. * This work was supported by NIAID Grant AI058944 from the National Insti-…”

“…Several studies have shown that the ribosomal protein L18a interacts with viral protein and eukaryotic initiation factor-3 and facilitates internal re-initiation of translation in cytomegalovirus and hepatitis C virus (12,(32)(33)(34). Our results indicate that this phenomenon is conserved in HTLV-I.…”

“…10B) (data not shown), suggesting that protein complex formation between p30 and L18a is not simply due to overexpression of these proteins. Numerous viral proteins have been shown (12,(32)(33)(34) to associate with nucleolin, which is the major constituent of the nucleolus. When we transfected a nucleolin expression vector along with p30, we did not detect any interactions between the two proteins (data not shown), again suggesting that protein complexes formed between p30 and L18a are specific.…”

Dengue virus NS1 protein interacts with the ribosomal protein RPL18: This interaction is required for viral translation and replication in Huh-7 cells

“…It has been described that the three ribosomal proteins have extraribosomal functions. For example, RPL18 plays an important role in translation of some viruses such as the cauliflower mosaic virus (Leh et al, 2000), while the RPL18A protein interacts with the internal ribosomal entry site (IRES) of Hepatitis C virus (Dhar et al, 2006), a member of the Flavivididae family. Additionally, the RPL7 has been involved in the anchoring of the ribosome to the endoplasmic reticulum membranes (Wu et al, 2007).…”

Deletion of a subgroup of ribosome-related genes minimizes hypoxia-induced changes and confers hypoxia tolerance

“…The mammalian homolog of Rpl20A is the ribosome protein L18a. It has been suggested that L18a may interact with RNA and promote translation (20). Rsm22 also has a mammalian homolog, suggesting that it is important for the function of the mitochondrial ribosome (96).…”