Ribosome Transfer RNA

In the cytoplasm the codons of mRNA are translated into amino acids via the concerted action of the ribosomes, transfer RNA (tRNA), and a large protein complex. In addition to the mature RNA sequence (capped and polyadenylated) other structural elements located in the 5 and 3 untranslated regions (UTRs) of the mRNA may influence its translation. 

The structure resembles that of a tRNA by molecular mimicry. The sequence Gly-Gly-Gln, present in both eukaryotes and prokaryotes, occurs at the end of the structure corresponding to the acceptor stem of a tRNA. This region binds a water molecule. Disguised as an aminoacyl-tRNA, the release factor may carry this water molecule into the peptidyl transferase center and, assisted by the catalytic apparatus of the ribosome, promote this water molecule s attack on the ester linkage, freeing the polypeptide chain. The detached polypeptide leaves the ribosome. Transfer RNA and messenger RNA remain briefly attached to the 70S ribosome until the entire complex is dissociated in a GTP-dependent fashion by ribosome release factor (RRF) and EF-G. Ribosome release factor is an essential factor for prokaryotic translation. 

On ribosomes, transfer RNA (tRNA) helps convert mRNA into protein. 

One of the main tasks of the DNA is to initiate the synthesis of proteins as and when they are needed. Proteins are synthesised in the ribosomes of the cell cytoplasm. DNA, however, is found in the cell nucleus. So how is the information contained in the DNA passed out of the cell nucleus and into the cytoplasm First, the DNA helix unfolds, and, in a process called transcription, a complementary strand of RNA is synthesised along a crucial part of one of the single DNA strands. This is the messenger RNA (mRNA) which leaves the cell nucleus and is transported into the manufacturing centres for proteins, the ribosomes. In the ribosome, transfer RNA (tRNA) delivers the amino acids required for polypeptide synthesis. The sequence of each group of three bases on the mRNA determines which amino acid is next in the peptide sequence. For example, the sequence AGC in the mRNA specifies the incorporation of the amino acid serine. This process is referred to as translation (Fig. 1.27). The genetic code, i.e. which sequence of bases in the DNA strand refers to which amino acid is given in Table 1.5. 

The translation step in the flow of genetic information results in the synthesis of proteins. The synthesis takes place when properly coded mRNA forms a complex with the component of a ribosome. Transfer RNA molecules carrying amino acids align themselves along the mRNA in an order representing the correct primary structure of the protein. The order is determined by the matching of complementary codons on the mRNA to anticodons on the tRNA. The amino acids sequentially bond together to form the protein, which then spontaneously forms characteristic secondary and tertiary structures. 

If the reaction occurs on ribosomes, transfer RNA must first attach to the ribosome. The amino acids that are attached to adjacent tRNA s become involved in peptide bond formation only after attachment. Thus, we need to discuss the mode of attachment of the tRNA to the ribosome and the mechanism of peptide bond formation. 

RNA Ribonucleic acid linear copolymers usually of four ribonucleotides. Three major types of RNA are synthesized in the cell ribosomal RNA (rRNA), the major component of ribosomes transfer RNA (tRNA), the adaptor for protein synthesis and messenger RNA (mRNA), which is required for information transfer. Other small RNAs with specialized functions are also synthesized in small amounts in both prokaryotic and eukaryotic cells. 

Transfer RNA (tRNA) Transfer RNAs are relatively small nucleic acids containing only about 70 nucleotides They get their name because they transfer ammo acids to the ribosome for incorporation into a polypeptide Although 20 ammo acids need to be transferred there are 50-60 tRNAs some of which transfer the same ammo acids Figure 28 11 shows the structure of phenylalanine tRNA (tRNA ) Like all tRNAs it IS composed of a single strand with a characteristic shape that results from the presence of paired bases m some regions and their absence m others... 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

Three-base codons on die mRNA corresponding to specific amino acids direct the sequence of building a protein. These codons are recognized by tRNAs (transfer RNAs) carrying die appropriate amino acids. Ribosomes are the machinery for protein syn diesis. 

In contrast, RNA occurs in multiple copies and various forms (Table 11.2). Cells contain up to eight times as much RNA as DNA. RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA). With these basic definitions in mind, let s now briefly consider the chemical and structural nature of DNA and the various RNAs. Chapter 12 elaborates on methods to determine the primary structure of nucleic acids by sequencing methods and discusses the secondary and tertiary structures of DNA and RNA. Part rV, Information Transfer, includes a detailed treatment of the dynamic role of nucleic acids in the molecular biology of the cell. 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

In the cytoplasm, the mRNA attaches to a ribosome and acts as a template for the construction of a protein with the proper amino acid sequence (a process known as translation ). Single amino acids are brought to the ribosome by transfer RNA molecules (tRNA) and added to the growing amino acid chain in the order instructed by the mRNA. Each time a nucleotide is added to the growing RNA strand, one molecule of ATP is broken down to ADP. Each time a tRNA binds an amino acid and each time the amino acid is added to the protein, additional ATP is broken down to ADP. Because proteins can contain many hundreds of amino acids, the cell must expend the energy in 1,000 or more ATP molecules to build each protein molecule. 

Transfer RNA (tRNA) transports amino acids to the ribosomes, where they are joined together to make proteins. 

Figure 1 Schematic drawing of the morphology of the ribosome. The ribosomal subunits are labeled, as are the approximate locations of their respective functional centers. The drawing is a transparent view from the solvent side of the small subunit. Transfer RNAs are shown in different binding states with the arrow indicating their direction of movement through the ribosome. The tRNA anticodon ends are oriented towards the viewer, whereas the 3-ends of the tRNAs are oriented towards the peptidyl transferase region on the large subunit. The letters h and b denote the head and body regions on the 30S subunit, respectively.

Mitochondria are unique organelles in man and higher animals in that they contain their own genome. Mitochondrial DNA (mtDNA) in humans is a small (16.5 kb), circular genome that encodes only 13 proteins, 22 transfer RNA (tRNA), and 2 ribosomal RNA (rRNA) molecules. mtDNA is inherited only from the mother and is present in multiple copies within one mitochondrion. 

In all prokaryotic and eukaryotic organisms, three main classes of RNA molecules exist messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA... 

The majority of the peptides in mitochondria (about 54 out of 67) are coded by nuclear genes. The rest are coded by genes found in mitochondrial (mt) DNA. Human mitochondria contain two to ten copies of a smaU circular double-stranded DNA molecule that makes up approximately 1% of total ceUular DNA. This mtDNA codes for mt ribosomal and transfer RNAs and for 13 proteins that play key roles in the respiratory chain. The linearized strucmral map of the human mitochondrial genes is shown in Figure 36-8. Some of the feamres of mtDNA are shown in Table... 

Both Ribosomal RNAs Most Transfer RNAs Are Processed From Larger Precursors... 

Figure 8.4 outlines the proeess of protein synthesis involving the ribosome, ruRNA, a series of aminoacyl transfer RNA (tRNA) moleeules (at least one for eaeh amino aeid)... 

Two different types of DNA occur in distinct locations in the living cell nuclear DNA in the cell s nucleus and mitochondrial DNA (mt-DNA) in the mitochondria (see Textbox 50). RNA occurs in several types messenger RNA, transfer RNA, ribosomal RNA, and others, all in the cytoplasm of the cells (see Table 85) (Bloomfield et al. 2000). 

As we have noted, the outcome of a virus infection is the synthesis of viral nucleic acid and viral protein coats. In effect, the virus takes over the biosynthetic machinery of the host and uses it for its own synthesis. A few enzymes needed for virus replication may be present in the virus particle and may be introduced into the cell during the infection process, but the host supplies everything else energy-generating system, ribosomes, amino-acid activating enzymes, transfer RNA (with a few exceptions), and all soluble factors. The virus genome codes for all new proteins. Such proteins would include the coat protein subunits (of which there are generally more than one kind) plus any new virus-specific enzymes. 

Not all the cellular DNA is in the nucleus some is found in the mitochondria. In addition, mitochondria contain RNA as well as several enzymes used for protein synthesis. Interestingly, mitochond-rial RNA and DNA bear a closer resemblance to the nucleic acid of bacterial cells than they do to animal cells. For example, the rather small DNA molecule of the mitochondrion is circular and does not form nucleosomes. Its information is contained in approximately 16,500 nucleotides that func-tion in the synthesis of two ribosomal and 22 transfer RNAs (tRNAs). In addition, mitochondrial DNA codes for the synthesis of 13 proteins, all components of the respiratory chain and the oxidative phosphorylation system. Still, mitochondrial DNA does not contain sufficient information for the synthesis of all mitochondrial proteins most are coded by nuclear genes. Most mitochondrial proteins are synthesized in the cytosol from nuclear-derived messenger RNAs (mRNAs) and then transported into the mito-chondria, where they contribute to both the structural and the functional elements of this organelle. Because mitochondria are inherited cytoplasmically, an individual does not necessarily receive mitochondrial nucleic acid equally from each parent. In fact, mito-chondria are inherited maternally. 

What is the importance of this enzyme family for the biogenesis problem These enzymes form the link between the protein world and the nucleic acid world . They catalyse the reaction between amino acids and transfer RNA molecules, which includes an activation step involving ATR The formation of the peptide bond, i.e., the actual polycondensation reaction, takes place at the ribosome and involves mRNA participation and process control via codon-anticodon interaction. 

Ribonucleic acid (RNA) Molecules including messenger RNA, transfer RNA, ribosomal RNA, or small RNA. RNA serves as a template for protein synthesis and other biochemical processes of the cell. The structure of RNA is similar to that of DNA except for the base thymidine being replaced by uracil. 

Transfer RNA (tRNA) RNA with a triplet nucleotide sequence that is complementary to the triplet nucleotide coding sequences of mRNA. tRNAs in protein synthesis bond with amino acids and transfer them to the ribosomes, where proteins are assembled according to the genetic code carried by mRNA... 

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