13.1 RNA, Consisting of a Single Strand of Ribonucleotides, Participates in a Variety of Cellular Functions

Before we begin our study of transcription, we will consider the past and present importance of RNA, review the structure of RNA, and examine some of the different types of RNA molecules.

An Early RNA World

Life requires two basic functions. First, living organisms must be able to store and faithfully transmit genetic information during reproduction. Second, they must have the ability to catalyze the chemical transformations that drive life processes. A long-held belief was that the functions of information storage and chemical transformation are handled by two entirely different types of molecules: genetic information is stored in nucleic acids, whereas chemical transformations are catalyzed by protein enzymes. This biochemical dichotomy created a dilemma. Which came first: proteins or nucleic acids? If nucleic acids carry the coding instructions for proteins, how could proteins be generated without them? Because nucleic acids are unable to copy themselves, how could they be generated without proteins? If DNA and proteins each require the other, how could life begin?

This apparent paradox was answered in 1981 when Thomas Cech and his colleagues discovered that RNA can serve as a biological catalyst. They found that RNA from the protozoan Tetrahymena thermophila can excise 400 nucleotides from its RNA in the absence of any protein. Other examples of catalytic RNAs have now been discovered in different types of cells. Called ribozymes, these catalytic RNA molecules can cut out parts of their own sequences, connect some RNA molecules together, replicate others, and even catalyze the formation of peptide bonds between amino acids. The discovery of ribozymes complements other evidence suggesting that the original genetic material was RNA.

Self-replicating ribozymes probably first arose between 3.5 billion and 4 billion years ago and may have begun the evolution of life on Earth. Early life was probably an RNA world, with RNA molecules serving both as carriers of genetic information and as catalysts that drove the chemical reactions needed to sustain and perpetuate life. These catalytic RNAs may have acquired the ability to synthesize proteinbased enzymes, which are more-efficient catalysts. With enzymes taking over more and more of the catalytic functions, RNA probably became relegated to the role of information storage and transfer. DNA, with its chemical stability and faithful replication, eventually replaced RNA as the primary carrier of genetic information. Nevertheless, RNA is either produced by or plays a vital role in many biological processes, including transcription, replication, RNA processing, and translation. Research in the past 15 years has also determined that newly discovered small RNA molecules play a fundamental role in many basic biological processes, demonstrating that life today is still very much an RNA world. These small RNA molecules will be discussed in more detail in Chapter 14.

CONCEPTS

Early life probably centered on RNA, which served as the original genetic material and as biological catalysts.

The Structure of RNA

RNA, like DNA, is a polymer consisting of nucleotides joined together by phosphodiester bonds (see Chapter 10 for a discussion of RNA structure). However, there are several important differences in the structures of DNA and RNA. Whereas DNA nucleotides contain deoxyribose sugars, RNA nucleotides have ribose sugars (Figure 13.1a). With a free hydroxyl group on the 2′-carbon atom of the ribose sugar, RNA is degraded rapidly under alkaline conditions. The deoxyribose sugar of DNA lacks this free hydroxyl group; so DNA is a more-stable molecule. Another important difference is that thymine, one of the two pyrimidines found in DNA, is replaced by uracil in RNA.

Figure 13.1: RNA has a primary and a secondary structure.

A final difference in the structures of DNA and RNA is that RNA usually consists of a single polynucleotide strand (Figure 13.1b), whereas DNA normally consists of two polynucleotide strands joined by hydrogen bonding between complementary bases (although some viruses contain double-stranded RNA genomes, as discussed in Chapter 9). Although RNA is usually single stranded, short complementary regions within a nucleotide strand can pair and form secondary structures (see Figure 13.1b). These RNA secondary structures are often called hairpin-loop or stem-loop structures. When two regions within a single RNA molecule pair up, the strands in those regions must be antiparallel, with pairing between cytosine and guanine and between adenine and uracil (although occasionally guanine pairs with uracil).

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The formation of secondary structures plays an important role in RNA function. Secondary structure is determined by the base sequence of the nucleotide strand, so different RNA molecules can assume different structures. Because their structure determines their function, RNA molecules have the potential for tremendous variation in function. With its two complementary strands forming a helix, DNA is much more restricted in the range of secondary structures that it can assume and so has fewer functional roles in the cell. Similarities and differences in DNA and RNA structures are summarized in Table 13.1. TRY PROBLEM 14

Characteristic DNA RNA
Composed of nucleotides Yes Yes
Type of sugar Deoxyribose Ribose
Presence of 2′-OH group No Yes
Bases A, G, C, T A, G, C, U
Nucleotides joined by phosphodiester bonds Yes Yes
Double or single stranded Usually double Usually single
Secondary structure Double helix Many types
Stability Stable Easily degraded
Table : Table 13.1: The structures of DNA and RNA compared

Classes of RNA

RNA molecules perform a variety of functions in the cell. Ribosomal RNA (rRNA) and ribosomal protein subunits make up the ribosome, the site of protein assembly. We’ll take a more-detailed look at the ribosome in Chapter 14. Messenger RNA (mRNA) carries the coding instructions for polypeptide chains from DNA to a ribosome. After attaching to the ribosome, an mRNA molecule specifies the sequence of the amino acids in a polypeptide chain and provides a template for joining amino acids. Large precursor molecules, which are termed pre-messenger RNAs (pre-mRNAs), are the immediate products of transcription in eukaryotic cells. Pre-mRNAs are modified extensively before becoming mRNA and exiting the nucleus for translation into protein. Bacterial cells do not possess pre-mRNA; in these cells, transcription takes place concurrently with translation.

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Transfer RNA (tRNA) serves as the link between the coding sequence of nucleotides in the mRNA and the amino acid sequence of a polypeptide chain. Each tRNA attaches to one particular type of amino acid and helps to incorporate that amino acid into a polypeptide chain (discussed in Chapter 15).

Additional classes of RNA molecules are found in the nuclei of eukaryotic cells. Small nuclear RNAs (snRNAs) combine with small protein subunits to form small nuclear ribonucleoproteins (snRNPs, affectionately known as “snurps”). Some snRNAs participate in the processing of RNA, converting pre-mRNA into mRNA. Small nucleolar RNAs (snoRNAs) take part in the processing of rRNA.

A class of very small and abundant RNA molecules, termed microRNAs (miRNAs) and small interfering RNAs (siRNAs), are found in eukaryotic cells and carry out RNA interference (RNAi), a process in which these small RNA molecules help trigger the degradation of mRNA or inhibit its translation into protein. More will be said about RNA interference in Chapter 14. Recent research has uncovered another class of small RNA molecules called Piwi-interacting RNAs (piRNAs; named after Piwi proteins, with which they interact). Found in mammalian testes, these RNA molecules are similar to miRNAs and siRNAs; they are thought have a role in suppressing the expression of transposable elements (see Chapter 18) in reproductive cells. Recently, an RNA interference-like system has been discovered in prokaryotes, in which small CRISPR RNAs (crRNAs) assist in the destruction of foreign DNA molecules. Some of the different classes of RNA molecules are summarized in Table 13.2.

Class of RNA Cell Type Location of Function in Eukaryotic Cells* Function
Ribosomal RNA (rRNA) Bacterial and eukaryotic Cytoplasm Structural and functional components of the ribosome
Messenger RNA (mRNA) Bacterial and eukaryotic Nucleus and cytoplasm Carries genetic code for proteins
Transfer RNA (tRNA) Bacterial and eukaryotic Cytoplasm Helps incorporate amino acids into polypeptide chain
Small nuclear RNA (snRNA) Eukaryotic Nucleus Processing of pre-mRNA
Small nucleolar RNA (snoRNA) Eukaryotic Nucleus Processing and assembly of rRNA
MicroRNA (miRNA) Eukaryotic Nucleus and cytoplasm Inhibits translation of mRNA
Small interfering RNA (siRNA) Eukaryotic Nucleus and cytoplasm Triggers degradation of other RNA molecules
Piwi-interacting RNA (piRNA) Eukaryotic Nucleus and cytoplasm Suppresses the transcription of transposable elements in reproductive cells
CRISPR RNA (crRNA) Prokaryotic Assists destruction of foreign DNA
*All eukaryotic RNAs are synthesized in the nucleus.
Table : Table 13.2: Location and functions of different classes of RNA molecules

CONCEPTS

RNA differs from DNA in that RNA possesses a hydroxyl group on the 2′-carbon atom of its sugar, contains uracil instead of thymine, and is usually single stranded. Several classes of RNA exist within bacterial and eukaryotic cells.

CONCEPT CHECK 1

Which class of RNA is correctly paired with its function?

  1. Small nuclear RNA (snRNA): processes rRNA
  2. Transfer RNA (tRNA): attaches to an amino acid
  3. MicroRNA (miRNA): carries information for the amino acid sequence of a protein
  4. Ribosomal RNA (rRNA): carries out RNA interference