The single-stranded RNA chromosomes of many viruses function as mRNAs for the synthesis of viral proteins. They are replicated in the host cell by an RNA-dependent RNA polymerase (RNA replicase). All RNA viruses—with the exception of retroviruses—must encode a protein with RNA-dependent RNA polymerase activity, either because the host cells lack such an enzyme or because the RNA genome structure of a virus imposes specialized enzymatic requirements.

The RNA replicase of most RNA bacteriophages has a molecular weight of ~210,000 and consists of four subunits. One subunit (Mr 65,000) is the product of the replicase gene encoded by the viral RNA and has the active site for replication. The other three subunits are host proteins normally involved in host-cell protein synthesis: the E. coli elongation factors Tu (Mr 45,000) and Ts (Mr 34,000) (which ferry amino acyl–tRNAs to ribosomes) and the protein S1 (an integral part of the 30S ribosomal subunit). These three host proteins may help the RNA replicase locate and bind to the 3′ ends of the viral RNAs.

The RNA replicase isolated from Qβ-infected E. coli cells catalyzes the formation of an RNA complementary to the viral RNA, in a reaction equivalent to that catalyzed by DNA-dependent RNA polymerases. New RNA strand synthesis proceeds in the 5′ → 3′ direction by a chemical mechanism identical to that used in all other nucleic acid synthetic reactions that require a template. RNA replicase requires RNA as its template and will not function with DN It lacks a separate proofreading endonuclease activity and has an error rate similar to that of RNA polymerase. Unlike the DNA and RNA polymerases, RNA replicases are specific for the RNA of their own virus; the RNAs of the host cell are generally not replicated. This explains how RNA viruses are preferentially replicated in the host cell, which contains many other types of RN

RNA-dependent RNA polymerases are not limited to viruses. Enzymes of this type are found in plants, protists, fungi, and some simpler animals, but not in insects or mammals. Those found in the genomes of eukaryotes generally play a role in the metabolism of another class of small RNAs, called small interfering RNAs (siRNAs), which participate in gene regulation.