The Central Dogma: An Introduction
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The document summarizes the central dogma of molecular biology: DNA is transcribed into RNA, which is then translated into protein. It describes the processes of DNA replication, transcription of DNA to mRNA, and translation of mRNA to proteins using tRNAs and ribosomes. Mutations are explained as changes to the DNA sequence that can alter protein production through frameshift or substitution errors. Recent research has found transcriptional exclusion of mutated alleles at the single-cell level.
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The Central Dogma: An Introduction
- 1. THE CENTRAL DOGMA GARRY D. LASAGA
- 3. THE CENTRAL DOGMA DNA is the genetic material within the nucleus. Replication creates new copies of DNA. Transcription creates an RNA using DNA information. Translation creates a protein using RNA information. Cytoplasm Nucleus DNA RNA Protein Replication Transcription Translation
- 4. The DNA
- 5. REPLICATION DNA Replication is semi- conservative. Each newly synthesized molecule contains 1 “parent template” strand and 1 new “daughter” strand.
- 6. TRANSCRIPTION: RNA Synthesis RNA is an important type of nucleic acid that plays several roles in the production of protein RNA is necessary to carry the instructions of the DNA out of the nucleus and to the ribosomes.
- 7. Two Types of Nucleic Acids
- 9. TRANSCRIPTION It is the mechanism by which a template strand of DNA is utilized by specific RNA polymerases to generate one of the 4 different types of RNA.
- 10. Types of RNA 1. mRNA (messenger RNA) 2. tRNA (transfer RNA) 3. rRNA (ribosomal RNA) 4. snRNA (small nuclear RNA)
- 11. TRANSCRIPTION DNA is used as a template for creation of RNA using the RNA polymerase. DNA 5’ 3’ 5’ 3’ GTCATTCGG CAGTAAGCC
- 12. TRANSCRIPTION RNA polymerase reads the nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule in a 5’ to 3’ direction that looks like the coding strand. CAGTAAGCC
- 13. TRANSCRIPTION The new RNA molecule is formed by incorporating nucleotides that are complementary to the template strand. DNA coding strand DNA
- 14. Initiation of Transcription Transcription begins at the 3’ end of the gene in a region called the promoter. The promoter recruits TATA protein, a DNA binding protein, which in turn recruits other proteins. TATA binding protein TATA CCCGG Transcription begins Promoter Gene sequence to be transcribed TATA boxTranscription factor
- 15. The Transcription Process RNA synthesis involves separation of the DNA strands and synthesis of an RNA molecule in the 5' to 3' direction by RNA polymerase, using one of the DNA strands as a template.
- 16. Complete Transcription of an RNA Molecule Transcription begins at the promoter, proceeds through the coding region, and ends at the terminator.
- 18. Codon A triplet of adjacent nucleotides in the messenger RNA chain that codes for a specific amino acid in the synthesis of a protein molecule. Each codon corresponds to a single amino acid (or stop signal), and the full set of codons is called the genetic code.
- 19. The Genetic Code All organisms use the same 20 aa Each codon specifies a particular aa
- 20. TRANSLATION: Protein Synthesis The process of reading the RNA sequence of an mRNA and creating the amino acid sequence of a protein. Transcription Codon CodonCodon Translation DNA GT T AC CA TG DNA template strand mRNA U AG GAA CC U Messenger RNA Protein Lysine Serine Valine Polypeptide (amino acid sequence)
- 21. TRANSLATION The language of nucleic acids in translated into the language of proteins Nucleic acids have a 4 letter language Proteins have a 20 letter language
- 22. TRANSLATION The “Players” Messenger RNA (mRNA) Ribosomes Transfer RNA (tRNA) Amino Acids
- 23. mRNA Synthesized in transcription Composed of Codons Codons are 3-base sequences of mRNA
- 24. Transfer RNA In the cytoplasm, a ribosome attaches to the mRNA and translates its message into a polypeptide. The process is aided by transfer RNAs. Amino acid attachment site Anticodon RNA polynucleotide chain
- 25. Ribosomes Made of rRNA and protein 2 subunits (large and small) form a 3D groove
- 26. Amino acids There are 20 amino acids, each with a basic structure Amino acids are held together by peptide bonds
- 27. Translation has 3 steps 1. Initiation 2. Elongation 3. Termination
- 28. Step 1. Initiation 1 Initiator tRNA mRNA binding site Start codon Small ribosomal subunit 2 P site Large Ribosomal subunit A site **mRNA, a specific tRNA, and the ribosome subunits assemble during initiation
- 29. Initiation Leader sequence mRNA 5’ ’3 mRNA AUG GGAUUCGUC CGA AUGUAAG Small ribosomal subunit Assembling to begin translation Met UAC Initiator tRNA
- 30. Step 2. Elongation CUA Met mRNA ’5 3’ Amino acid Large ribosomal subunit CCU tRNA Ribosome Gly CUUU GGGG GG AA A A A P A
- 31. Elongation CUA Met mRNA 5’ 3’ CCU Gly UU CUGG GGGGA A A A A P A
- 32. Elongation mRNA ’5 ’3 CU U Lys Lengthening polypeptide (amino acid chain ) AA C Cys U UU CG G GGGG AAA A A P A
- 33. Elongation mRNA ’5 CUUU GGGGGG A AA AA UAA Stop codon C UG Arg CU U Lys Release factor P A
- 34. Termination mRNA ’5 Stop codon Ribosome reaches stop codon C UG Arg U U U C GGGG GG AA AA A UAA Release factorP A
- 35. Termination Release factorP Once stop codon is reached, elements disassemble. A
- 36. The Genetic Code All organisms use the same 20 aa Each codon specifies a particular aa
- 37. The Genetic Code is a triplet code Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
- 38. Mutations Normally, the genetic code is translated and the correct protein is formed from a long chain of amino acids. Translation of codons is dependent on the reading frame, or a grouping of codons in a gene transcript. AAU GCG GAC UAC GGC AAC GCC
- 39. Mutation Any change in the nucleotide sequence of DNA It may involve large sections of chromosomes or single base pairs Mutations can change the reading frame of a gene transcript.
- 40. Mutation Normal Hemoglobin Sickle Cell Hemoglobin DNA GGA CTT GCA GGA CAT GCA mRNA CCU GAA CGU CCU GUA CGU A.A. PRO GLU ARG PRO VAL ARG Changes in one or a few bases is called a Point Mutation 2 Types: Substitution or Insertion/Deletions
- 41. Mutation Deletion or insertion mutations are most disruptive because they change the reading frame, causing a frame shift. Substitution mutations have varied impact on amino acid sequences.
- 43. What causes Mutations? Errors in DNA Replication Errors in chromosome crossover in meiosis Mutagens Mutagens are physical or chemical factors that cause mutations UV Radiation and X-Rays Chemicals like DDT
- 44. Recent research paper (2015) “Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles” by Wengi Li, R., et al. It showed a novel relationship between genotype and phenotype SCTG
- 45. References What is the ‘Central Dogma’? Retrieved from https://www.frontiersin.org/articles/10.3389/fgene.20 15.00305/full The Central Dogma BioCoach Activity. Retrieved from http://www.phschool.com/science/biology_place/bio coach/transcription/overview.html
Editor's Notes
- The Central Dogma of Molecular Biology Describes the flow of genetic information from DNA to RNA to Proteins. It involves the processes of DNA replication, transcription and translation. Molecular biology studies the composition, structure and interactions of cellular molecules such as nucleic acids and proteins that carry out the biological processes essential for the cell’s functions and maintenance.
- The DNA contains the complete genetic information that defines the structure and function of an organism. Proteins are formed using the genetic code of the DNA. Three different processes are responsible for the inheritance of genetic information and for its conversion from one form to another : 1. Replication – a process where the double-stranded DNA is duplicated to give identical copies. This process perpetuates (preserve) the genetic information. The keyword is DNA duplicates. 2. Transcription – a DNA segment (gene) is read and transcribed into a single-stranded sequence of RNA. It is also known as RNA synthesis. The RNA moves from the nucleus into the cytoplasm. 3. Translation – is aka protein synthesis. It is where the RNA sequence is translated into a sequence of amino acids as the protein is formed.
- The DNA is mostly found in the nucleus of a cell.. This type of is known as chromosomal DNA. The image shows that the DNA, which has a molecular shape of a double helix is contained within a chromosome. The chromosome is a threadlike part of the cell that carries hereditary information in the form of genes. The DNA is made up of nucleotides bases that includes adenine, cytosine, guanine and thymine. They are found in pairs, adenine is to thymine and guanine to cytosine.
- A: number of strands; B: kind of sugar; D: base used. DNA can be catalytic while RNA is not. Catalysis is an increase in the rate of chemical reaction.
- A: number of strands; B: kind of sugar; D: base used. DNA can be catalytic while RNA is not. Catalysis is an increase in the rate of chemical reaction.
- The RNA Polymerase is an enzyme that is responsible for copying a DNA sequence into an RNA sequence during transcription.
- mRNA: encodes amino acid sequence of a polypeptide. tRNA: brings amino acids to ribosomes during translation rRNA - Ribosomal RNA: With ribosomal proteins, makes up the ribosomes, the organelles that translate the mRNA snRNA: With proteins, forms complexes that are used in RNA processing in eukaryotes Messenger RNA carries the actual code that specifies the amino acid sequence in a polypeptide (protein)
- A protein-coding gene consists of a promoter, a coding sequence and a terminator. The promoter is a base-pair sequence that specifies where transcription begins. The coding sequence includes coding information for the polypeptide chain specified by the gene. The terminator specifies the end of the mRNA transcript.
- In complementary base pairing, A, T, G, and C on the template DNA strand specify U, A, C, and G, respectively, on the RNA strand being synthesized.
- Genes are made up of promoter regions and alternating regions of introns (noncoding sequences) and exons (coding sequences). The production of a functional protein involves the transcription of the gene from DNA into RNA, the removal of introns and splicing together of exons, the translation of the spliced RNA sequences into a chain of amino acids, and the posttranslational modification of the protein molecule.
- A codon is a sequence of three DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis. DNA and RNA molecules are written in a language of four nucleotides; meanwhile, the language of proteins includes 20 amino acids. Codons provide the key that allows these two languages to be translated into each other.
- Genetic code - the biochemical basis of heredity consisting of codons in DNA and RNA that determine the specific amino acid sequence in proteins and appear to be uniform for nearly all known forms of life
- During translation, the ribosome reads three bases (a codon) at a time from the RNA and translates them into one amino acid.
- Physically, mRNA is a strand of nucleotides known as ribonucleic acid, and is single-stranded. Codon is a sequence of 3 DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis.
- TRNA – functions to bring the amino acid to ribosomes during translation.
- 2 major sites: P site---holds the growing polypeptide A site---new amino acids enter here
- The mRNA binds to ribosome. The start codon AUG and anticodon with Methionine bind a P site. The A site is open and ready to receive new tRNAs. Translation begins at start codon (AUG=methionine)
- Elongation - adding new amino acids. Elongation: the ribosome uses the tRNA anticodon to match codons to amino acids and adds those amino acids to the growing peptide chain
- Elongation: the ribosome uses the tRNA anticodon to match codons to amino acids and adds those amino acids to the growing peptide chain
- Elongation: the ribosome uses the tRNA anticodon to match codons to amino acids and adds those amino acids to the growing peptide chain
- Elongation: the ribosome uses the tRNA anticodon to match codons to amino acids and adds those amino acids to the growing peptide chain
- Translation ends at the stop codon UAA, UAG or UGA
- Within each cell the genetic information flows from – DNA to RNA to protein. The information carried within the DNA dictates the end product (protein) that will be synthesized. This information is the genetic code. Genetic code - the biochemical basis of heredity consisting of codons in DNA and RNA that determine the specific amino acid sequence in proteins and appear to be uniform for nearly all known forms of life
- Substitutions of 1st or 2nd base in codon almost always changes the amino acid Substitution of 3rd base in codon does not always change the amino acid
- Many mutations are harmful and cause the organism to die or function incorrectly. Some mutations are beneficial and help the organism to survive. (Peppered Moths) If mutations are present in gametes, they can be passed on to offspring.
- SCTG – allows DNA and RNA sequencing to be performed concurrently on the same single cells taken from a cell population treated with a mutagen. The method allowed the authors to prove the tendency of the transcriptional machinery in the cell to avoid transcribing DNA strands harboring a newly induced mutation.