Gene Expression: From DNA to Protein and Mutation Mechanisms

Comprehensive vocabulary flashcards covering the molecular mechanisms of gene expression, translation and transcription cycles, cellular targeting, prokaryotic versus eukaryotic differences, and types of genetic mutations.

Gene

A specific location on a chromosome that encodes a program of the genetic code and provides the instructional information to synthesize an RNA transcript, which may either code for a protein or possess its own independent cellular function.

Allele

A distinct variant of a gene characterized by nucleotide sequence differences that can produce functional differences; sexually reproducing individuals possess up to two alleles (one from each parent), whereas a population's gene pool may contain many.

Central Dogma

The foundational principle of molecular biology stating that genetic information stored in DNA is preserved through replication, copied into messenger RNA through transcription, and subsequently decoded into a functional protein through translation at ribosomes.

Transcription

The enzymatic synthesis of an RNA molecule from a DNA template strand by RNA polymerase, which reads the template DNA strand in the $3' \rightarrow 5'$ direction and synthesizes the RNA molecule in the $5' \rightarrow 3'$ direction.

Template Strand

The non-coding strand of double-stranded DNA that RNA polymerase reads in the $3' \rightarrow 5'$ direction to assemble a complementary, antiparallel RNA transcript.

Coding Strand

The strand of DNA whose base sequence matches the synthesized RNA transcript (with thymine in place of uracil) and runs in the $5' \rightarrow 3'$ direction.

Promoter

A specific DNA sequence situated at the $5'$ end of the coding strand that marks the start of a gene and serves as the binding site for RNA polymerase and transcription factors to initiate transcription.

Enhancer

A regulatory DNA sequence located upstream of a gene in eukaryotes that binds activator proteins, interacting via DNA bending and mediator proteins to stabilize RNA polymerase assembly at the promoter.

Terminator

A specific nucleotide sequence positioned at the $3'$ end of a gene that signals RNA polymerase to stop synthesis and dissociate from the DNA.

$\alpha$-Amanitin

A cyclic octapeptide toxin produced by the death cap mushroom (Amanita phalloides) that exerts lethal poisoning by directly binding to and inhibiting eukaryotic RNA polymerase.

Codon

A contiguous sequence of three RNA nucleotides read consecutively from the $5'$ end to the $3'$ end of an mRNA molecule without intervening spaces, each coding for a specific amino acid in a polypeptide's primary structure or serving as a stop signal.

Transfer RNA (tRNA)

A single-stranded RNA molecule folded into a precise three-dimensional structure stabilized by specific complementary base pairs, featuring a $3'\text{ ACC}$ amino acid attachment site at one pole and a complementary anticodon loop at the opposite pole.

Anticodon

A sequence of three nucleotides on a tRNA molecule that base-pairs complementarily and antiparallelly with a matching three-base codon on the mRNA transcript inside the ribosome.

Aminoacyl-tRNA Synthetase

A specific enzyme responsible for "charging" a tRNA by covalently attaching its corresponding amino acid to the $3'$ attachment site at the expense of ATP.

Ribosome

A large macromolecular assembly composed of ribosomal RNA ($\text{rRNA}$) and proteins whose catalytic peptidyl transferase activity is executed by a specific ribosomal RNA nucleotide at its active site rather than a protein enzyme.

A Site (Aminoacyl Site)

The functional site on a complete ribosome that receives an incoming aminoacyl-tRNA delivering the next amino acid specified by the mRNA codon during elongation.

P Site (Peptidyl Site)

The ribosomal site occupied by the tRNA linked to the growing polypeptide chain immediately prior to peptide bond transfer to the tRNA situated in the adjacent aminoacyl site.

E Site (Exit Site)

The ribosomal site that holds the deacylated (uncharged) tRNA after peptide bond transfer, immediately before it departs the ribosome to be re-charged in the cytoplasm.

Signal Peptide

An initial amino acid sequence at the N-terminal end of a nascent polypeptide that dictates the destination of the protein to the rough endoplasmic reticulum for membrane integration, organelle delivery, or cellular secretion.

Signal Recognition Particle (SRP)

A cytosolic ribonucleoprotein complex that recognizes and binds the emerging signal peptide of a nascent protein, escorting the translating ribosome to an SRP receptor on the rough endoplasmic reticulum membrane.

Polycistronic mRNA

A single messenger RNA transcript found in prokaryotes that carries the coding sequences for multiple adjacent genes, allowing concurrent translation of several distinct proteins.

Monocistronic mRNA

A messenger RNA molecule typical of eukaryotes that contains the coding information for only a single polypeptide chain.

Pre-mRNA Processing

The nuclear modification of eukaryotic primary transcripts prior to cytoplasmic export, consisting of the addition of a $5'$ cap, the addition of a $3'$ poly(A) tail, and the excision of non-coding introns with the ligation of coding exons.

Silent Mutation

A point mutation that substitutes a single nucleotide in a coding sequence without altering the encoded amino acid residue, thereby producing no phenotypic change in the resulting protein.

Nonsense Mutation

A point mutation that converts an amino acid-specifying codon into a premature STOP codon ($\text{UAA}$, $\text{UAG}$, or $\text{UGA}$), causing truncated and typically nonfunctional polypeptides.

Conservative Missense Mutation

A point mutation in which a nucleotide substitution changes the codon to specify a different amino acid with chemical properties (e.g., charge, polarity, size) similar to the original amino acid, often preserving native protein function.

Non-conservative Missense Mutation

A point mutation in which a nucleotide change causes the substitution of an amino acid possessing distinctly different chemical properties compared to the wild-type residue, often significantly altering protein structure and activity.

Sickle Cell Mutation

A non-conservative missense point mutation in the $\beta$-globin gene where a single nucleotide change ($\text{CTC} \rightarrow \text{CAC}$ on DNA; $\text{GAG} \rightarrow \text{GUG}$ on mRNA) substitutes an acidic, hydrophilic glutamic acid with a non-polar valine, producing sticky non-polar sites that cause deoxygenated hemoglobin to aggregate.

$\beta$-Thalassemia

A group of inherited blood conditions caused by diverse point mutations in the human $\beta$-globin gene cluster (occurring in promoters, $5'\text{ UTR}$, introns, splice sites, or exons) that reduce or abolish synthesis of functional $\beta$-globin chains, resulting in malformed red blood cells.

Frameshift Mutation

A mutation caused by the insertion or deletion of one or more nucleotides in a quantity not divisible by three, disrupting the downstream codon reading frame and causing extensive missense alterations or premature nonsense termination.

Triplet Repeat Mutation

A type of mutation caused by DNA polymerase slippage during replication that increases the number of trinucleotide repeats within a genomic domain over successive generations.

Huntington's Disease Repeat Thresholds

The diagnostic categorization of $(\text{CAG})_n$ trinucleotide repeats in the Huntingtin gene: $<28$ repeats is normal (unaffected), $28\text{--}35$ repeats is intermediate (unaffected), $36\text{--}40$ repeats confers reduced penetrance ($\pm$ affected), and $>40$ repeats confers full penetrance (affected).

Chromosomal Translocation

A structural chromosomal alteration in which a broken fragment of one chromosome is relocated and joined to a non-homologous chromosome.

Chromosomal Inversion

A chromosomal rearrangement resulting from two breaks within a single chromosome, followed by a $180^\circ$ rotation of the intervening segment and its reinsertion into the chromosome.

Benzo[a]pyrene

A major environmental chemical mutagen present in tobacco smoke that damages genetic material by covalently binding directly to DNA nucleotides and disrupting double helix structure.