pubmed-article:18669441 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C0035668 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C1514562 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C1704973 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C0439855 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C2360340 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C1328949 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C0439599 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C1444662 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C0205224 | lld:lifeskim |
pubmed-article:18669441 | lifeskim:mentions | umls-concept:C1704788 | lld:lifeskim |
pubmed-article:18669441 | pubmed:issue | 9 | lld:pubmed |
pubmed-article:18669441 | pubmed:dateCreated | 2008-8-29 | lld:pubmed |
pubmed-article:18669441 | pubmed:abstractText | Tertiary or higher-order RNA motifs that regulate replication of positive-strand RNA viruses are as yet poorly understood. Using Japanese encephalitis virus (JEV), we now show that a key element in JEV RNA replication is a complex RNA motif that includes a string of three discontinuous complementary sequences (TDCS). The TDCS consists of three 5-nt-long strands, the left (L) strand upstream of the translation initiator AUG adjacent to the 5'-end of the genome, and the middle (M) and right (R) strands corresponding to the base of the Flavivirus-conserved 3' stem-loop structure near the 3'-end of the RNA. The three strands are arranged in an antiparallel configuration, with two sets of base-pairing interactions creating L-M and M-R duplexes. Disrupting either or both of these duplex regions of TDCS completely abolished RNA replication, whereas reconstructing both duplex regions, albeit with mutated sequences, fully restored RNA replication. Modeling of replication-competent genomes recovered from a large pool of pseudorevertants originating from six replication-incompetent TDCS mutants suggests that both duplex base-pairing potentials of TDCS are required for RNA replication. In all cases, acquisition of novel sequences within the 3'M-R duplex facilitated a long-range RNA-RNA interaction of its 3'M strand with either the authentic 5'L strand or its alternative (invariably located upstream of the 5' initiator), thereby restoring replicability. We also found that a TDCS homolog is conserved in other flaviviruses. These data suggest that two duplex base-pairings defined by the TDCS play an essential regulatory role in a key step(s) of Flavivirus RNA replication. | lld:pubmed |
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pubmed-article:18669441 | pubmed:language | eng | lld:pubmed |
pubmed-article:18669441 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:18669441 | pubmed:citationSubset | IM | lld:pubmed |