September 1, 1996Microbiological Reviews250 citationsOpen Access
View Full PaperRNA-protein interactions in regulation of picornavirus RNA translation
Key Result
Cellular proteins, including La and polypyrimidine tract-binding protein, functionally interact with picornavirus internal ribosome entry site (IRES) elements to regulate viral RNA translation.
Structured PICO
P
Population
in vitro translation systems (rabbit reticulocyte lysate) and picornavirus RNA (cardiovirus, aphthovirus, enterovirus, rhinovirus)
E
Exposure
Supplementation with additional cellular proteins (e.g., La, polypyrimidine tract-binding protein)
O
Outcome
Translation efficiency and production of aberrant initiation products
Cellular proteins such as La and polypyrimidine tract-binding protein play a functional role in interacting with picornavirus IRES elements to regulate RNA translation.
Limitations
- The function and significance of many observed RNA-protein interactions are not always known.
Abstract
The translation of picornavirus RNA occurs by a cap-independent mechanism directed by a region of about 450 nucleotides from the 5' untranslated region, termed an internal ribosome entry site (IRES). Internal initiation of protein synthesis occurs without any requirement for viral proteins. Furthermore, it is maintained when host cell protein synthesis is almost abolished. By using in vitro translation systems, two distinct families of IRES elements which have very different predicted RNA secondary structures have been defined. The cardiovirus and aphthovirus elements function very efficiently in rabbit reticulocyte lysate, whereas the enterovirus and rhinovirus elements function poorly in this system. However, supplementation of this translation system with additional cellular proteins can stimulate translation directed by the enterovirus and rhinovirus RNAs and reduce production of aberrant initiation products. The characterization of cellular proteins interacting with the picornavirus IRES is a major focus of research. Many different protein species can be observed to interact with regions of the IRES by in vitro analyses, e.g., UV cross-linking. However, the function and significance of many of these interactions are not always known. For two proteins, La and the polypyrimidine tract-binding protein, evidence has been obtained for a functional role of their interaction with IRES elements.