The small 3.2-kb-long DNA genomes of hepadnaviruses are replicated by reverse transcription of an RNA intermediate. This RNA 'pregenome' contains important signals that control critical steps of replication that include RNA packaging, initiation of reverse transcription, and elongation of minus strand DNA. Transcribed with terminally redundant ends, from a covalently closed circular DNA, pregenomic RNA also contains signals that regulate the conditional use of a polyadenylation site. To function as a pregenome the transcript must not enter the splicing pathway and therefore bears signals that permit splicing-independent egress from the nucleus and transport to ribosomes where it exerts its other role as a messenger RNA for the synthesis of capsid and polymerase polypeptides. Translation, in turn, demands signals that maintain the stoichiometry of about 200 capsid proteins per molecule of polymerase synthesized.
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