GCT1.MB - L1. The “central dogma”.pptx

The central dogma: DNA → RNA → protein ⮚ Essential Cell Biology by Bruce Alberts, 5th edition ⮚ KARP’S CELL AND MOLECULAR BIOLOGY  An Overview of the Flow of Information through the Cell The Central Dogma...

The central dogma: DNA → RNA → protein ⮚ Essential Cell Biology by Bruce Alberts, 5th edition ⮚ KARP’S CELL AND MOLECULAR BIOLOGY  An Overview of the Flow of Information through the Cell The Central Dogma Proposed by Francis Crick 1958 The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. RNA‐based enzymatic catalysis is an essential part of the machinery for synthesizing proteins. While DNA duplication is driven by protein enzymes in modern organisms, the ability of DNA and RNA to base pair with free nucleotides suggests a scenario in which an RNA sequence spontaneously formed that was then able to self‐replicate, ultimately giving rise to many self‐propagating copies of itself. This is known as the “ RNA world ” hypothesis, which proposes that life began as RNA.  An Overview of the Flow of Information through the Cell /cont./ The Central Dogma The first meaningful insight into gene function was gained by Archibald Garrod, a physician who reported in 1908 that the symptoms exhibited by persons with certain rare inherited diseases were caused by the absence of specific enzymes. Garrod had discovered the relationship between a genetic defect, a specific enzyme, and a specific metabolic condition. He called such diseases “inborn errors of metabolism.” One of the diseases investigated by Garrod was alcaptonuria , a condition readily diagnosed because the urine becomes dark on exposure to air. Garrod found that persons with alcaptonuria lacked an enzyme in their blood that oxidized homogentisic acid, a compound formed during the breakdown of the amino acids phenylalanine and tyrosine. As homogentisic acid accumulates, it is excreted in the urine and darkens in color when oxidized by air. A cell can express different genes at different rates. The portions of the DNA that are not transcribed are shown in gray.  An important discovery Retro viruses (e.g. HIV - human immunodeficiency virus) carry RNA as their genetic information. When they invade their host cell they convert their RNA into a DNA copy using reverse transcriptase. Thus the central dogma is modified: DNA ↔ RNA → Protein  Introns and Exons—Additional Complexity in Eukaryotic Genes The protein-coding regions of almost all eukaryotic genes are organized as a series of separate bits interspersed with noncoding regions. The protein-coding regions of the split genes are called exons. The regions between are called introns, short for intervening sequences. In Figure we can see the structure of the β- globin gene, which contains three exons and two introns. Introns are often very long compared to exons. Messenger RNA complementary to the DNA is synthesized, then the introns are spliced out before the mRNA leaves the nucleus. This means that a gene is much longer than the mRNA that ultimately codes for the protein. The name exon derives from the fact that these are the regions of the gene that, when transcribed into mRNA, exit from the nucleus. Most protein-coding genes occur only once in the genome and are called single-copy genes. The human α- and β-globin gene family clusters. Adults only express α, β, and δ, and of these the expression of δ is very low. The exon/intron boundaries of the β- globin gene are indicated at the bottom. Most eukaryotic genes in contrast to typical bacterial genes, the coding sequences (exons) are interrupted by noncoding DNA (introns). The gene must have (Exon; start signals; stop signals; regulatory control elements). Protein synthesis four steps: ▪ Transcription ▪ RNA processing ▪ Translation ▪ Post-translation processing  Transcription: The synthesis of a strand of mRNA (and other RNAs) Transcription (or RNA synthesis) is the process whereby the information held in the nucleotide sequence of DNA is transferred to RNA. The three major classes of RNA are ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA). All play key roles in protein synthesis. Genes encoding mRNAs are known as protein-coding genes. A gene is said to be expressed when its genetic information is transferred to mRNA and then to protein. small interfering RNAs (siRNAs)  RNA Three major types of eukaryotic RNAs—mRNAs, rRNAs, and tRNAs—are derived from precursor RNA molecules that are considerably longer than the final RNA product. The initial precursor RNA is equivalent in length to the full length of the DNA transcribed and is called the primary transcript , or pre‐RNA. The corresponding segment of DNA from which a primary transcript is transcribed is called a transcription unit. Primary transcripts do not exist within the cell as naked RNA but become associated with proteins even as they are synthesized. Primary transcripts typically have a fleeting existence, being processed into smaller, functional RNAs by a series of “cut‐and paste” reactions. RNA processing requires a variety of small RNAs (90 to 300 nucleotides long) and their associated proteins. ⮚Messenger RNA (mRNA)