Biochemistry,  Cell biology,  Genetics

RNA

Structurally speaking, ribonucleic acid (RNA), is quite similar to DNA. However, whereas DNA molecules are typically long and double-stranded, RNA molecules are much shorter and are typically single-stranded. RNA molecules perform a variety of roles in the cell but are mainly involved in the process of protein synthesis (translation) and its regulation.

RNA Structure

RNA is typically single-stranded and is made of ribonucleotides that are linked by phosphodiester bonds. A ribonucleotide in the RNA chain contains ribose (the pentose sugar), one of the four nitrogenous bases (A, U, G, and C), and a phosphate group. The subtle structural difference between the sugars gives DNA added stability, making DNA more suitable for storage of genetic information, whereas the relative instability of RNA makes it more suitable for its more short-term functions. The RNA-specific pyrimidine uracil forms a complementary base pair with adenine and is used instead of the thymine used in DNA. Even though RNA is single-stranded, most types of RNA molecules show extensive intramolecular base pairing between complementary sequences within the RNA strand, creating a predictable three-dimensional structure essential for their function.

RNA Structure
(a) Ribonucleotides contain the pentose sugar ribose instead of the deoxyribose found in deoxyribonucleotides. (b) RNA contains the pyrimidine uracil in place of thymine found in DNA.
RNA structure
(a) DNA is typically double-stranded, whereas RNA is typically single-stranded. (b) Although it is single-stranded, RNA can fold upon itself, with the folds stabilized by short areas of complementary base pairing within the molecule, forming a three-dimensional structure.

Types of RNA: mRNA, rRNA and tRNA

In both prokaryotes and eukaryotes, there are three main types of RNA – messenger RNA or mRNA, ribosomal or rRNA, and transfer RNA or tRNA.

types-of-rna

Messenger RNA (mRNA)

mRNA accounts for just 5% of the total RNA in the cell. mRNA is the most heterogeneous of the 3 types of RNA in terms of both base sequence and size. It carries the genetic code copied from the DNA during transcription in the form of triplets of nucleotides called codons. Each codon specifies a particular amino acid, but one amino acid can be coded by many different codons. Although there are 64 possible codons or triplet bases in the genetic code, only 20 of them represent amino acids; there are also 3 stop codons.

As part of post-transcriptional processing in eukaryotes, the 5’ end of mRNA is capped with a guanosine triphosphate nucleotide, which helps in mRNA recognition during translation or protein synthesis. Similarly, the 3’ end of an mRNA has a poly-A tail or multiple adenylate residues added to it, which prevent enzymatic degradation of mRNA. Both 5’ and 3’ end of an mRNA imparts stability to the mRNA.

Ribosomal RNA (rRNA)

rRNAs are found in the ribosomes and account for 80% of the total RNA present in the cell. Ribosomes are composed of a large subunit called the 50S and a small subunit called the 30S, each of which has its own rRNA molecules. Different rRNAs present in the ribosomes include small rRNAs and large rRNAs, which denote their presence in the small and large subunits of the ribosome.

rRNAs combine with proteins in the cytoplasm to form ribosomes, which act as the site of protein synthesis and has the enzymes needed for the process. These complex structures travel along the mRNA molecule during translation and facilitate the assembly of amino acids to form a polypeptide chain. They bind to tRNAs and other molecules that are crucial for protein synthesis.

In bacteria, the small and large rRNAs contain about 1500 and 3000 nucleotides, respectively, whereas in humans, they have about 1800 and 5000 nucleotides, respectively. However, the structure and function of ribosomes is largely similar across all species.

Transfer RNA (tRNA)

tRNA is the smallest of the 3 types of RNA having about 75-95 nucleotides. tRNAs are an essential component of translation, where their main function is the transfer of amino acids during protein synthesis. Therefore they are called transfer RNAs. Each of the 20 amino acids has a specific tRNA that binds with it and transfers it to the growing polypeptide chain. tRNAs also act as adapters in the translation of the genetic sequence of mRNA into proteins. Therefore they are also called adapter molecules.

tRNAs have a clover leaf structure which is stabilized by strong hydrogen bonds between the nucleotides. Apart from the usual 4 bases, they normally contain some unusual bases mostly formed by methylation of the usual bases, for example, methyl guanine and methylcytosine.

Functions of RNA in Protein Synthesis

Cells access the information stored in DNA by creating RNA to direct the synthesis of proteins through the process of translation. Proteins within a cell have many functions, including building cellular structures and serving as enzyme catalysts for cellular chemical reactions that give cells their specific characteristics. The three main types of RNA directly involved in protein synthesis are messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).

In 1961, French scientists François Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA. Evidence supporting their hypothesis was gathered soon afterwards showing that information from DNA is transmitted to the ribosome for protein synthesis using mRNA. If DNA serves as the complete library of cellular information, mRNA serves as a photocopy of specific information needed at a particular point in time that serves as the instructions to make a protein.

The mRNA carries the message from the DNA, which controls all of the cellular activities in a cell. If a cell requires a certain protein to be synthesized, the gene for this product is “turned on” and the mRNA is synthesized through the process of transcription. The mRNA then interacts with ribosomes and other cellular machinery to direct the synthesis of the protein it encodes during the process of translation. mRNA is relatively unstable and short-lived in the cell, especially in prokaryotic cells, ensuring that proteins are only made when needed.

RNA function
A generalized illustration of how mRNA and tRNA are used in protein synthesis within a cell.

rRNA and tRNA are stable types of RNA. In prokaryotes and eukaryotes, tRNA and rRNA are encoded in the DNA, then copied into long RNA molecules that are cut to release smaller fragments containing the individual mature RNA species. In eukaryotes, synthesis, cutting, and assembly of rRNA into ribosomes takes place in the nucleolus region of the nucleus, but these activities occur in the cytoplasm of prokaryotes. Neither of these types of RNA carries instructions to direct the synthesis of a polypeptide, but they play other important roles in protein synthesis.

Ribosomes are composed of rRNA and protein. As its name suggests, rRNA is a major constituent of ribosomes, composing up to about 60% of the ribosome by mass and providing the location where the mRNA binds. The rRNA ensures the proper alignment of the mRNA, tRNA, and the ribosomes; the rRNA of the ribosome also has an enzymatic activity (peptidyl transferase) and catalyzes the formation of the peptide bonds between two aligned amino acids during protein synthesis. Although rRNA had long been thought to serve primarily a structural role, its catalytic role within the ribosome was proven in 2000. Scientists in the laboratories of Thomas Steitz (1940–) and Peter Moore (1939–) at Yale University were able to crystallize the ribosome structure from Haloarcula marismortui, a halophilic archaeon isolated from the Dead Sea. Because of the importance of this work, Steitz shared the 2009 Nobel Prize in Chemistry with other scientists who made significant contributions to the understanding of ribosome structure.

Transfer RNA is the third main type of RNA and one of the smallest, usually only 70–90 nucleotides long. It carries the correct amino acid to the site of protein synthesis in the ribosome. It is the base pairing between the tRNA and mRNA that allows for the correct amino acid to be inserted in the polypeptide chain being synthesized (Figure 4). Any mutations in the tRNA or rRNA can result in global problems for the cell because both are necessary for proper protein synthesis.

tRNA structure
A tRNA molecule is a single-stranded molecule that exhibits significant intracellular base pairing, giving it its characteristic three-dimensional shape.
mRNArRNAtRNA
StructureShort, unstable, single-stranded RNA corresponding to a gene encoded within DNALonger, stable RNA molecules composing 60% of ribosome’s massShort (70-90 nucleotides), stable RNA with extensive intramolecular base pairing; contains an amino acid binding site and a mRNA binding site
FunctionServes as intermediary between DNA and protein; used by ribosome to direct synthesis of protein it encodesEnsures the proper alignment of mRNA, tRNA, and ribosome during protein synthesis; catalyzes peptide bond formation between amino acidsCarries the correct amino acid to the site of protein synthesis in the ribosome

RNA as Hereditary Information

Although RNA does not serve as the hereditary information in most cells, RNA does hold this function for many viruses that do not contain DNA. Thus, RNA clearly does have the additional capacity to serve as genetic information. Although RNA is typically single-stranded within cells, there is significant diversity in viruses. Rhinoviruses, which cause the common cold; influenza viruses; and the Ebola virus are single-stranded RNA viruses. Rotaviruses, which cause severe gastroenteritis in children and other immunocompromised individuals, are examples of double-stranded RNA viruses. Because double-stranded RNA is uncommon in eukaryotic cells, its presence serves as an indicator of viral infection. The implications for a virus having an RNA genome instead of a DNA genome are discussed in more detail in Viruses.

 

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