遗传 进化与生态学 10 - RNA Processing and Translation
本期的内容是 RNA转录后的加工与修饰 以及 翻译。本文集的这一部分是遗传、进化与生态学 Genetics, Evolution, and Ecology. 这门课理论上建议在阅读完文集的第一部分的内容之后再开始学习，但基础不足的朋友也可以尝试阅读喔~
这一部分的主要内容均来自 Prof. Angela J. Roles 的 BIOL 200 课程，因此本文集的这一部分均不会标记为原创。但由于文本来源不清晰，UP主还是一个字一个字码出来的文章，本文禁止非授权的转载，谢谢！
Lesson 10: RNA Processing and Translation
[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).
RNA processing: after initial transcription, before translation
[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?
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)
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!
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).
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.
[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...
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?
[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).
[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.
How does the HbS allele give rise to the sickle shape?
