Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element

Firth, Andrew E.; Wills, Norma M.; Gesteland, Raymond F.; Atkins, John F.

Numerous studies have shown that the identity of the 3 0 -adjacent nucleotide influences stop codon leakiness in both prokaryotes and eukaryotes and, correspondingly, there is considerable bias in the identity of the nucleotide at this position for natural gene terminators (10) (11) (12) (13) (14) (15) (16) . Of great interest was the discovery that RT of the coat protein (CP) gene terminator of the phage Qb yields a greatly extended protein that is important for viral propagation (17, 18) . Shortly afterwards, studies that utilized purified yeast suppressor tRNAs in in vitro experiments found that several plant viruses, including tobacco mosaic tobamovirus (TMV), also utilize RT to express their replicase proteins (19) (20) (21) . Similarly murine leukemia gammaretrovirus (MuLV), whose relevant sequence is identical to that in xenotropic MuLV-related virus (XMRV), utilizes RT of the gag gene terminator to allow ribosomes to enter the pol gene and synthesize the Gag-Pol polyprotein that is the source of viral reverse transcriptase (22, 23) . MuLV Pol binds to the translation release factor, eRF1, and non-interacting mutants of Pol failed to synthesize adequate levels of Gag-Pol to permit replication (24) . This raises the possibility of temporal control of RT (25) . The efficiency of RT in the Drosophila gene kelch also appears to be developmentally regulated (26) . Two other Drosophila genes are known to employ RT-headcase and out-at-first-though another approximately 150 candidate cases have recently been identified via comparative genomic approaches utilizing sequences from 12 Drosophila species (27) (28) (29) . Although some of these candidates may actually be cases of alternative splicing or RNA editing, the indication is that utilized RT may be significantly more common in cellular organisms than previously supposed.