4.3

Learning Objectives

• 4.3 Analyze the different levels of RNA structure, and how they are related to RNA function.

The Two Key Functions of RNA

• The first living molecule must have performed two key functions:

  • Carry Information

  • Catalyze Reactions

  • These reactions must promote the molecule's own replication.

• Initial conflict between these functions:

  • Information storage requires:

  • Regularity

  • Stability

  • Catalysis requires:

  • Variation in chemical composition

  • Flexibility in shape

• Key Question: How can a molecule achieve both functions?

  • Answer: The answer lies in the structure of RNA.

Structural Differences Between RNA and DNA

• Primary Structure:

  • Consists of four types of nitrogenous bases extending from a sugar backbone, similar to DNA.

  • Key Differences:

  • Sugar Type:

    • RNA contains ribose instead of deoxyribose as in DNA.

  • Pyrimidine Bases:

    • Thymine (found in DNA) is absent in RNA.

    • RNA contains uracil instead.

• Importance of Ribose:

  • The hydroxyl group on the 2' carbon of ribose is much more reactive than the hydrogen on the same carbon in deoxyribose.

  • This reactivity leads to potential breaks in the RNA sugar-phosphate backbone during molecule folding.

  • RNA's structure makes it less stable than DNA but may also support various catalytic activities.

RNA Secondary Structure

• Like DNA, most RNA molecules form secondary structures due to complementary base pairing between purine and pyrimidine bases.

• Base Pairing in RNA:

  • Adenine pairs with uracil forming 2 hydrogen bonds.

  • Guanine pairs forming 3 hydrogen bonds with cytosine.

• Differences in Secondary Structure:

  • In RNA, complementary base pairing often occurs within the same strand rather than between two different strands (as in DNA).

  • Antiparallel Orientation:

  • When bases form pairs on overlapping parts of the strand, the sugar-phosphate strands are antiparallel.

  • Hydrogen bonding results in structures resembling a helical structure, akin to DNA but formed from a single strand.

• Stem and Loop Configuration:

  • If folds occur with unpaired bases, secondary structures may resemble stems and loops.

• Types of RNA Secondary Structures:

  • RNA can form various secondary structures involving different lengths and arrangements of base pairs.

  • Similar to the alpha helices and beta-pleated sheets in proteins, RNA forms spontaneously due to hydrophobic interactions and stabilized by hydrogen bonding and base stacking interactions.

Tertiary Structure of RNA

• RNA molecules can attain tertiary structures when secondary structures fold into more complex shapes.

• Example:

  • The pseudonaut structure illustrates how three-dimensional shapes can form by base pairing between distant regions of folded RNA.

• Tertiary structures allow RNA molecules with different base sequences to have varied overall shapes and chemical properties.

• RNA exhibits greater diversity in size, shape, and reactivity compared to DNA.

The Versatility of RNA

• Role of RNA in Cells:

  • RNA functions like a multi-tool with various roles.

  • RNA, as a nucleic acid, folds into complex three-dimensional shapes similar to proteins.

• Structural flexibility allows RNA to function in various tasks:

  • Acts as an intermediate in the central dogma between DNA and proteins (messenger RNA, mRNA).

  • Transmits information necessary for synthesizing polypeptides.

• Research has uncovered the diverse functions of RNA in cells:

  • Regulates mRNA production from DNA

  • Processes and edits information within messages

  • Catalyzes protein synthesis

  • Additional roles explored in Chapters 17, 18, and 19.

RNA's Role in the Origin of Life

• Key Hypothesis:

  • RNA may have functioned both as a catalyst and as a molecule containing information at the origin of life.

• Catalytic Function of RNA:

  • Despite having only four nucleotides compared to the 20 amino acids in proteins, RNA's structural and chemical complexity allows it to catalyze various reactions.

• Nobel Prize in Chemistry (1989):

  • Awarded to Sidney Altman and Thomas Cech for discovering catalytic RNAs known as ribozymes.

  • Ribozymes catalyze reactions similar to those performed by protein enzymes, such as hydrolysis and condensation of phosphodiester linkages in RNA.

• Multiple ribozymes have been identified, serving essential functions in cells, including as components of ribosomes, which polymerize amino acids into polypeptides.

The Importance of Ribozymes

• Active Site:

  • For a ribozyme to catalyze a reaction, substrates must be positioned in an environment conducive to the reaction.

  • The active site of ribozymes has structural similarities to the active sites of protein enzymes.

• This critical relationship between structure and function underlines the significance of ribozymes in the study of the origin of life.

• Prior to this discovery, the scientific community largely believed that only proteins could act as cellular catalysts.

  • The emergence of the ribozyme capable of forming phosphodiester bonds suggests that RNA could replicate itself, qualifying it as a potential first living entity.

Experimental Evidence for RNA as a Forebearer of Life

• The transcript ends with an inquiry regarding the existence of experimental evidence supporting the hypothesis that RNA could serve as the first living molecule capable of catalyzing its own replication.