BIOMEDICINE: Turning Positive into Negative

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Science  30 Mar 2001:
Vol. 291, Issue 5513, pp. 2517c
DOI: 10.1126/science.291.5513.2517c

Many medically important viruses have positive strand RNA genomes, so called because the genome is the messenger RNA that is translated into protein. Successful replication of these viruses requires that the positive strand RNA be copied faithfully into a negative strand, a process catalyzed by a replication complex containing a virally encoded RNA-dependent RNA polymerase. In the case of poliovirus, new insights into this reaction are emerging from in vitro replication systems, which allow researchers to manipulate the RNA template and protein components.

Using mutant poliovirus RNA templates, Barton et al. find that a cloverleaf structure at the 5' end of the RNA is essential for replication. Because negative strand synthesis is initiated at the 3' end of the RNA, this suggests that the RNA template circularizes prior to replication, a configuration that may help to stabilize the RNA and clear it of ribosomes. In another study, Hobson et al. find that the poliovirus polymerase forms a higher order oligomeric structure that is critical for its function. Polymerase-polymerase interactions were required for substrate RNA binding and for formation of the enzyme's catalytic site. Together, these results reinforce the notion that poliovirus RNA replication in infected cells is carried out by an efficient and highly ordered machinery. — PAK

Acknowledgments

EMBO J. 20, 1439 (2001); EMBO J. 20, 1153 (2001).

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