We know that information is not transferred directly from DNA to protein, because, in a eukaryotic cell, DNA is in the nucleus, whereas protein is synthesized in the cytoplasm. Information transfer from DNA to protein requires an intermediate. That intermediate is RNA.

Although DNA and RNA are nucleic acids, RNA differs from DNA in that (1) it is usually single stranded rather than a double helix, (2) its nucleotides contain the sugar ribose rather than deoxyribose, (3) it has the pyrimidine base uracil rather than thymine, and (4) it can serve as a biological catalyst.

The similarity of RNA to DNA suggests that the flow of information from DNA to RNA relies on the complementarity of bases, which is also the key to DNA replication. A template DNA strand is copied, or transcribed, into either a functional RNA (such as transfer RNA or ribosomal RNA), which is never translated into polypeptides, or a messenger RNA, from which proteins are synthesized.

In prokaryotes, all classes of RNA are transcribed by a single RNA polymerase. This multisubunit enzyme initiates transcription by binding to the DNA at promoters that contain specific sequences at −35 and −10 bases before the transcription start site at +1. After being bound, RNA polymerase locally unwinds the DNA and begins incorporating ribonucleotides that are complementary to the template DNA strand. The chain grows in the 5′-to-3′ direction until one of two mechanisms, intrinsic or rho dependent, leads to the dissociation of the polymerase and the RNA from the DNA template. As we will see in Chapter 9, in the absence of a nucleus, prokaryotic RNAs that encode proteins are translated while they are being transcribed.

In eukaryotes, there are three different RNA polymerases; only RNA polymerase II transcribes mRNAs. Overall, the phases of initiation, elongation, and termination of RNA synthesis in eukaryotes resemble those in prokaryotes. However, there are important differences. RNA polymerase II does not bind directly to promoter DNA, but rather to GTFs, one of which recognizes the TATA sequence in most eukaryotic promoters. RNA polymerase II is a much larger molecule than its prokaryotic counterpart. It contains numerous subunits that function not only to elongate the primary RNA transcript, but also to coordinate the extensive processing events that are necessary to produce the mature mRNA. These processing events are 5′ capping, intron removal and exon joining by spliceosomes, and 3′ cleavage followed by polyadenylation. Part of the RNA polymerase II core, the carboxy terminal domain (CTD), is positioned ideally to interact with the nascent RNA as it emerges from polymerase. Through the CTD, RNA polymerase II coordinates the numerous events of RNA synthesis and processing.

Discoveries of the past 20 years have revealed the importance of new classes of functional RNAs. Once thought to be a lowly messenger, RNA is now recognized as a versatile and dynamic participant in many cellular processes. The discovery of self-splicing introns demonstrated that RNA can function as a catalyst, much like proteins. Since the discovery of these ribozymes, the scientific community has begun to pay more attention to RNA. Small nuclear RNAs, the noncoding RNAs in the spliceosome, are now recognized to provide the catalytic activity to remove introns and join exons. The twentieth century ended with the discovery that two other classes of functional RNA, miRNA and siRNA, associate with RNA-induced silencing complexes (RISC) and target complementary cellular mRNA for repression (in the case of miRNA) or for destruction (in the case of siRNA).