Objectives Unit Ten:  Synthesis of RNA and Protein:  Transcription
and Translation

1.  Define the following terms and utilize these terms in an appropriate context:
anticodon                      codon                           consensus sequence           exon
intron                              messenger RNA         promoter                                ribosome
transcription                  translation                    wobble hypothesis                enhancer
primer                            up mutation                  down mutation

2.  Describe in general the two main functions of DNA.

3.  Explain and illustrate with diagrams how mRNA synthesis occurs.

4.  Explain and illustrate with diagrams the location and "anatomy" of a ribosome.

5.  Describe the arrangement of nucleotide bases in a tRNA molecule, and the basic
functions of the two "ends" of the molecule.

6.  Given the tRNA anticodon, and a mRNA code chart, determine which activated
amino acid would become attached to that particular tRNA molecule.

7.  Outline, using diagrams, the attachment of the proper amino acid-tRNA combination
to the initiator codon of a mRNA strand at the P-site of a 40S ribosome particle.

8.  Outline translation of the genetic code by listing in their proper sequence the events
which must occur, starting with amino acid activation and ending with the release of the
completed polypeptide.

9.  Explain that the genetic code, stored in DNA, is transferred to RNa, where it is
used to direct the synthesis of polypeptide chains.

10.  Explain what is meant by the descriptions of the genetic code being, degenerate,
unambiguous, nonoverlapping, and comma-free.

11.  Describe the observed pattern of degeneracy in the code involving only the third
letter of a triplet series, leading to the proposal of the Wobble Hypothesis.

12.  Define and differentiate between transcription and translation.

13.  Relate transcription and translation- RNA and protein biosynthesis, respectively-
are fundamental processes essential to the expression of genetic information.

14.  Illustrate the fact that the processes of transcription and translation are more complex
in eukaryotes than in prokaryotes.

15.  Contrast the roles of tRNA and mRNA during translation and list all enzymes that
participate in the transcription and translation process.

16.  Differentiate between the locations and roles of the codon and anticodon.

17.  If given a sequence of DNA sense strand:
-predict the mRNA sequence it will generate.
-using the mRNA codon sequence and the coding dictionary, predict the corresponding
polypeptide   sequence as determined by the tRNA anticodons.

18.  If given a sequence of a short wild-type protein as well as various mutant forms of the
protein:
-using the coding dictionary construct a potential mRNA sequence
-describe the general type of mutation in each case
-indicate the specific base-pair change that occurred for each mutation, assuming these
mutations resulted   from single base-pair changes.

Resources:  Text Chapter 12 and 13, Cartoon Guide pgs. 129-157
 

 Synthesis of RNA and Protein: Transcription and Translation

    Clear that proteins are end products of many genes -gene expression

    Problem:     How is DNA, a nucleic acid, able to specify a protein (How is info transferred?)
                          How can DNA, confined to the nucleus, synthesize protein in the cytoplasm?

    DNA copied in small pieces and removed from nucleus--> RNA

       Transcription- process by which RNA molecules are synthesized on DNA template. (mRNA)

       Translation- RNA sequence, written in genetic code, translates code into polypeptide chains.
            tRNA- transfer RNA- serve as adaptors between codons of mRNA and amino acids
                specified by them.

    Codon/Anticodon
        -rely on base-pairing affinities between complementary base
        -transcribe one (sense strand) strand of DNA
        -triplet codon (3 base sequence on mRNA) pairs with anticodon triplet of tRNA
        -A.A.'s assembled at ribosome

            Garrod-relationship between inheritance and metabolic disease, "inborn errors of
                metabolism"

            Beadle & Tatum- one gene, one enzyme

            Pauling & Itano- revised to one gene, one polypeptide

    Central Dogma (rigidly held principle or doctrine)- DNA serves as a template for its
own replication and for transcription of complementary RNA.

    RNA- RiboNucleic Acid
        1. single stranded
        2. ribose sugar instead of deoxyribose
        3. pyrimidine bases uracil rather than thymine.

    Transcription: RNA synthesis
        Info flow from DNA ---> protein suggests:
            1. since DNA in nucleus and protein synthesis is in cytoplasm. . . DNA does
                    not participate in protein synthesis (Eukaryote)

        Concept that RNA is intermediate suggests:
            2. RNA synthesized in nucleus (Eukaryotes) where DNA is found & is chemically
                similar to DNA
            3. following its synthesis, most RNA migrates to cytoplasm
            4. amount of RNA generally proportional to amount of protein in a cell.

General features of RNA synthesis (copied from the segment of DNA that constitutes
a gene)
        1. Precursors
            ATP, adenosine triphosphate (Adenine)
            UTP, uridine triphosphate (Uracil)
            CTP, cytidine triphosphate (Cytosine)
            GTP, guanosine triphosphate (Guanine)

            Differ from DNA only in sugar and uracil replaces thymine

        2. Formation of RNA, sugar-phosphate bond between nucleotides 5'--> 3', same as
            DNA except RNA  polymerase used. (if assembly in 5'--> 3' then how does it read,
            transcribe, the DNA? 3' --> 5'

        3. Sequence of bases on RNA determined by sequence on DNA.
            *difference between DNA polymerase and RNA polymerase is that RNA polymerase
              is able to initiate chain growth without primer

            *in any particular region of DNA only one strand serves as a template for RNA
                sense vs. missense (nonsense)

            -Promoter recognition RNA polymerase binds to DNA within a base sequence
                from 20-200 bases called a promoter

            many promoters have been isolated, sequence variation corresponds to different
            strangths of promoters.

            2 consensus sequences (bases most often observed) most often observed at a
                specific position

                *Pribnow box, -10 box, TATA box
                *-35 box

            Located "upstream" from start of transcription

            More closely promoter elements resemble consensus, the stronger the promoter.

            In Eukaryotes, enhancers interact w/ promoters to determine level of transcription

               down mutation- destroy matches w/ consensus sequence, weaken promoter
               up mutation- improves match w/ concensus sequence, strengthens promoter.

            -Chain initiation
                RNA polymerase initiates synthesis at consensus site, first nucleotide triphosphate
                placed at this site and synthesis begins in 5' --> 3' direction

            -Chain elongation
                RNA polymerase moves along DNA adding nucleotides.
                *remember, only one of the 2 DNA strands transcribed

            -Chain termination
                chain terminating sequence UAA, UGA, UAG

                inverted repeats, symmetrical about center, would read the same if rotated 180o

                Hair pins- symmetrical about center and is self complementary, can pair to form hairpin

    mRNA- Transcribes DNA
        -template strand of each gene corresponds to only one of the DNA strands
        -which DNA strand differs from gene to gene
        *Not all mRNA molecules transcribed from same DNA strand

    mRNA processing
        1. Translation rarely starts exactly at one end of RNA and proceeds to the other end.
        2. Section of untranslated RNA called leader, in some cases contains regulatory
            sequences.
        3. Coding sequence - specifies polypeptide chain, typical coding sequence
            500- 3000 bases long, depends on # of amino acids in chain
        4. "Cap"- terminal group necessary for ribosomes to bind with mRNA to begin
            protein synthesis
        5. Poly-A tail aids mRNA stability
        6. Initiation codon- AUG (methionine)
        7. Stop codons UAA, UAG, UGA; no tRNA exists to bind to these, interupts elongation
        8. Editing- excision of introns (junk)
 

Translation- translation of mRNA code into amino acid sequence
        A. rRNA- ribosomes, located in cytoplasm, endoplasmic retic. composed of RNA and
            protein (formed by DNA!)
            1. 2 subunits (Svedberg units) 60s particle and 40s particle (s refers to sedimentary
                rates in a centrifuge)
                P site- polypeptide, holds elongating chain
                A site- Amino acid, accepts incoming amino acids

        B. tRNA- transfer RNA, contains paired and unpaired bases

            -one end is anticodon (matches complementary mRNA codon)
            -other end is attached to a specific Amino acid

            Anticodon- pairs with mRNA codon

            tRNA responsible for translating mRNA into a specific amino acid sequence
            (polypeptide ---> protein)

        C. Amino Acids (20 naturally occurring)

           peptide formation

        D. translation takes place at ribosome
            40s unit contains Psite and Asite

            1. small subunit recognizes "cap" and initiator codon AUG
                    -initiator tRNA (w/ anticodon UAC) attaches to initiator
                    -large subunit attaches, translation begins

            2. elongation- tRNA w/ attached polypeptide chain is at Psite
                    -new tRNA w/ new AA arrives at Asite
                    --translocation: new AA ataches to chain, ribosome moves down

            3. mRNA translated until ribosome encounters stop codon

            4. polysome- more than one ribosome working to make protein

The Genetic Code
    -triplet, codons (code words) direct insertion of single amino acids to polypeptide chain

    General features:

        1. code is in linear form derived from DNA
        2. each "word" within mRNA contains 3 letters, thus code is triplet: each group of
            3 nucleotides (codon) codes for one amino acid.
            -if one nucleotide ---> one AA, then only 4 AA's
            -if two nucleotides ---> 42, only 16 AA's
            -if three nucleotides ---> 43 = 64, plenty to code for 20 *tRNA contains anticodon

        3. code is unambiguous, each triplet specifies only one AA

        4. code is degenerate, more than one triplet specifies for a given AA (this is the case
            for 18 of the 20AAs)

        5. code contains "start" (AUG) and "stop" (UAA, UGA, UAG)

        6. code is commaless, no internal punctuation. Once translation begins, each
            three nucleotides are read in turn.

        7. code is nonoverlapping, once translation begins any single nucleotide is part of
            only one triplet

        8. code is universal, with only minor exceptions, single coding dictionary is used by
            viruses, pro and eukaryotes.

Deciphering the code:
        Crick and others ---> Frame shift mutations
            insertions- induce changes (mutants)
            deletions- reversions to wild type

            Change and restoration of original reading frame

        Marshall, Nirenberg- RNA homopolymers
            poly U ---> phenyalanine
            poly C
            poly G
            poly A etc
            poly UG (RNA heteropolymers)

        Complete code pg 238

Degeneracy- most often first two letters are common for triplets of any amino acid

       Wobble hypothesis
            -first two more important than the third
            -less specific hydrogen bonding required for third
            -wobble would allow single tRNA species to pair w/ more than one triplet in mRNA
            -codes degeneracy would allow this to occur w/o changing amino acids

        Comparing coding assignments it appears that U at position #3 of tRNA may pair
            w/ A or G at #3 spot in mRNA

            -applying "wobble" rules, minimum of 30 tRNA needed
                Economy measure

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