遺傳 進化與生態(tài)學(xué) 10 - RNA Processing and Translation
本期的內(nèi)容是 RNA轉(zhuǎn)錄后的加工與修飾 以及 翻譯。本文集的這一部分是遺傳、進化與生態(tài)學(xué) Genetics, Evolution, and Ecology. 這門課理論上建議在閱讀完文集的第一部分的內(nèi)容之后再開始學(xué)習(xí)，但基礎(chǔ)不足的朋友也可以嘗試閱讀喔~
這一部分的主要內(nèi)容均來自 Prof. Angela J. Roles 的 BIOL 200 課程，因此本文集的這一部分均不會標(biāo)記為原創(chuàng)。但由于文本來源不清晰，UP主還是一個字一個字碼出來的文章，本文禁止非授權(quán)的轉(zhuǎn)載，謝謝！
Lesson 10: RNA Processing and Translation
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[1] RNA processing & Splicing
?RNA must be moved from the nucleus to the cytoplasm before translation can occur.
?RNA processing prepares the RNA strand for export to the nucleus
????- The pre-mRNA must be marked for nuclear export with stabilizing and signaling molecules.
????- The pre-mRNA must be spliced to remove introns (and possibly some exons).
????Note: Non-coding RNAs are not processed and not translated into protein. Instead, they function as RNAs; examples are ribosomal RNA (rRNA) and transfer RNA (tRNA).
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RNA processing: after initial transcription, before translation
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[2] Alternative splicing - One gene may encode several similar proteins
?The sequence of amino acids encoded in the exons of the mRNA specifies the shape and function of a given protein.
?Alternative splicing is when different subsets of the exons can be retained in the processed mRNA.
????- Each exon codes for multiple amino acids.
????- The shape and function of the protein will vary depending on which exons are included in the processed mRNA.
?This process is regulated: proteins present in the nucleus bind to specific nucleotides on the transcript, repressing or activating splicing of particular exons.
?In humans, ~95% of genes with >1 exon can be alternatively spliced.
[3] Codons: 3 nucleotides in mRNA specifies 1 amino acid
Triplet codons specify a particular amino acid (a.a.), in the 5’ to 3’ direction.
?Questions to consider...
?????What happens to the a.a. sequence if a mutation in the DNA deleted one nucleotide?
?????What if a mutation in the DNA added one nucleotide?
?????What if one nucleotide in the DNA mutated to a different nucleotide?
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Language of translation: codon table
? ? ?AUG = start codon and methionine
?????UAA, UAG, or UGA = stop codon
?????Code is partly redundant: some a.a. are specified by multiple codons
?????Wobble base: when the 3rd nucleotide is not needed to determine the a.a. (example: Leu, leucine)
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Codons, nucleotide sequence, and phenotype
?Why do we need to understand the relationship between nucleotides and amino acids?
????- For this class, we want to understand how changes to the DNA sequence can cause changes to visible phenotype.
????- When changes to DNA sequence alter amino acids, that can change the structure or function of a protein...
????- And changes to proteins can mean changes to phenotypes that we can see!
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Neutral evolution of DNA sequences
?IMPORTANT: Many (most?) nucleotide changes will not cause any kind of change to a protein or a phenotype.
?Most of the sequence in our genomes is NOT genes, it’s non-coding DNA. Changes here are unlikely to affect an organism’s phenotype.
?Many changes to gene sequences will also not change phenotype (will be neutral).
????- For example, if the amino acid is not altered (common for changes to the third nucleotide in a codon)
?Neutral changes are the most useful for building phylogenies because similarity for such changes is most likely due to common ancestry (and not convergent evolution).
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From RNA processing to translation
?Once our mRNA is mature (has been spliced and marked for nuclear export), we are ready to talk about what happens outside the nucleus.
?Translation is initiated in the cytoplasm
????- The mRNA has markers that specify where and when it should be translated.
?Functional RNAs and proteins must bind to the mRNA to recruit the ribosomal components and initiate translation.
?Ribosomes catalyze peptide bonds, reading the mRNA and then moving the correct amino acid from a tRNA to the growing polypeptide chain.
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[4] Ribosomes
Ribosome structure: protein and RNA. Ribosomes are the enzymes that read mRNA and build the polypeptide chain.
??Left part of the figure: lines are RNA chains while spheres are protein.
?The catalytic activity of some RNAs (ribozymes) may point to early mechanisms of transcription/translation...
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Polyribosomes: One mRNA can be translated multiple times, simultaneously.
?What might be a benefit of polyribosomes?
?If we know how much mRNA there is, can we predict how much protein is made?
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[5] Protein structure: different ways of describing proteins
?????Primary structure = the chain of amino acids in a single polypeptide;
?????Secondary structure = 3-D form of local sections of a polypeptide; examples: alpha helices and beta sheets;
?????Tertiary structure = full 3-D shape of a single polypeptide;
?????Quaternary structure = 3-D protein containing more than one polypeptide (multiple subunits).
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[6] Beta-globin Example
????Alleles to Phenotypes: β-globin in humans
????- The HbA allele: has a T/A pair in the 6th codon of the gene encoding?hemoglobin subunit beta (HBB); produces typical ‘round’ globin molecules.
? ? -?The HbS allele: has a A/T pair in the 6th codon of the Beta-globin gene;?produces globin molecules that polymerize under deoxygenation – forming rigid?fibers that cause sickle shaped red blood cells.
Glutamic acid is hydrophilic while Valine is hydrophobic.
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How does the HbS allele give rise to the sickle shape?
