A region of the 5' noncoding region of foot-and-mouth disease virus RNA directs efficient internal initiation of protein synthesis within cells: involvement with the role of L protease in translational control

Abstract

Plasmids encoding bicistronic mRNAs have been constructed and used to identify a region from the 5' noncoding region of foot-and-mouth disease virus (FMDV) which directs efficient internal initiation of protein synthesis within cells. The loss of about 30 nucleotides (nt) from the 5' terminus or about 50 nt from the 3' terminus of the 435-nt region completely abolished the activity of this region. The expression of the FMDV L protease severely inhibited the expression of other genes unless they were preceded by this element. The regulation of protein synthesis mediated by FMDV is discussed.

Conserved tertiary structure elements in the 5′ untranslated region of human enteroviruses and rhinoviruses

“…Results from a number of laboratories (Jang et al, 1988(Jang et al, , 1989Belsham and Brangwyn, 1990;Kuhn et a/., 1990;Pelletier and Sonenberg, 1988;Bienkowska-Szewczyk and Ehrenfeld, 1988;Jackson et a/., 1990)…”

Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure

“…These results led to the concept of internal initiation of protein synthesis becoming widely accepted. This activity has now been demonstrated for a member of each genus of the pieornavirus family including FMDV (Belsham and Brangwyn, 1990;Kuhn et al, 1990;Brown et al, 1991). The translation of both open reading frames from bicistronic mRNAs has become the favoured assay for internal initiation and allows the ready analysis of both cap-dependent and cap-independent translation directed by the 5'NCR of the picornaviruses at the same time.…”

“…Studies on the 5'NCR of FMDV using artificial bicistronic mRNAs have shown that a region of 435 bases immediately upstream from the first initiation site of F MDV is necessary and sufficient to direct internal initiation of protein synthesis within cells (Belsham and Brangwyn, 1990). Furthermore when cap-dependent protein synthesis was inhibited by the co-expression of the FMDV L protein (which induces the cleavage of the p220 cap-binding complex component) the expression of the first open reading frame was almost abolished while the expression of the open reading frame following the FMDV IRES continued.…”

“…Also within this region is the structure termed the internal ribosome entry sequence (IRES) comprising some 435 bases immediately upstream of the first AUG initiation codon (Belsham and Brangwyn, 1990;Kuhn et al, 1990). This element is also predicted to have an extensive secondary structure and will be discussed in some detail later.…”

Genetic analysis of picornaviruses

“…The 5' non-coding regions of picomaviral RNAs vary from 600-1200 nucleotides in length, and must perform at least two functions. At the 5' end of the viral mRNAs, sequences from 140-630, 403-811 and 369-805 in poliovirus [16], encephalomyocarditis virus [17] and foot-and-mouth disease virus [18,19], respectively, confer the ability for picomaviral RNAs to be translated in cells by the unusual mechanism of internal ribosome binding. RNA sequences and factors mediating this process are under intense scrutiny; the state of this research has been recently reviewed [20"].…”