Molecular Biology Terms Starting With T
Molecular Biology Glossary: T
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TATA Box
/ TAH-tah BOKS / · Named after the consensus nucleotide sequence T-A-T-A
TATA Box is a conserved AT-rich promoter sequence located approximately 25 to 30 base pairs upstream of the transcription start site that positions RNA polymerase II for accurate initiation of transcription.
The TATA box is recognized by TATA-binding protein, a subunit of the general transcription factor TFIID, which initiates assembly of the pre-initiation complex on the promoter. Its AT-rich sequence is easily unwound because adenine-thymine base pairs share only two hydrogen bonds, lowering the energy barrier for strand separation at transcription onset. Only about 24% of human genes contain a canonical TATA box; many promoters instead rely on alternative elements such as the initiator element or the downstream promoter element to direct transcription start-site selection.
Genes with TATA boxes tend to be tightly regulated and highly responsive to cellular signals, while TATA-less promoters often drive constitutively expressed housekeeping genes.
TATA-binding protein binds DNA in an unusual way: it inserts into the minor groove and bends the DNA by roughly 80 degrees, partially unwinding the double helix. No other general transcription factor contacts DNA in this manner.
Every human gene has a TATA box. Only about one in four human genes contains a canonical TATA box, and many promoters use entirely different sequence elements to recruit the transcription machinery.
The adenovirus major late promoter contains one of the most studied TATA box sequences in molecular biology. Researchers used this promoter in the 1980s to work out the stepwise assembly of the RNA polymerase II pre-initiation complex, identifying the ordered recruitment of TFIID, TFIIA, TFIIB, and other factors.
Telomerase
/ teh-LOM-er-aze / · Greek telos (end) + meros (part) + -ase (enzyme suffix)
Telomerase is an RNA-dependent DNA polymerase that synthesizes repetitive telomeric DNA sequences onto chromosome ends, counteracting the shortening that occurs with each round of replication.
Telomerase contains an integral RNA subunit that carries the template sequence used to add TTAGGG repeats onto the 3-prime overhang of human chromosomes. In most somatic cells, telomerase activity is repressed, so telomeres shorten by roughly 50 to 200 base pairs with each cell division until they reach a critical length that triggers senescence or apoptosis. Cancer cells frequently reactivate telomerase, which lets them divide without limit.
Elizabeth Blackburn, Carol Greider, and Jack Szostak shared the 2009 Nobel Prize in Physiology or Medicine for discovering telomeres and telomerase.
The ciliated protozoan Tetrahymena thermophila was the organism in which Carol Greider and Elizabeth Blackburn first identified telomerase activity in 1984. Tetrahymena was chosen because its macronucleus contains millions of tiny chromosomes, providing an exceptionally rich source of telomeric DNA for biochemical study.
Building Blocks of Nucleic Acids →Chromosome ends are copied perfectly by ordinary DNA polymerase alone. Standard DNA polymerases cannot replicate the very tip of a linear chromosome, so without telomerase or alternative lengthening mechanisms, chromosome ends shorten with every division.
Human germ cells and stem cells maintain telomerase activity to preserve telomere length across many cell divisions. Most differentiated somatic cells lack this activity, and their telomeres shorten measurably with age, with leukocyte telomeres averaging a loss of about 24 to 48 base pairs per year in adults.
Template Strand
/ TEM-plate strand / · Latin templum, pattern; Old English strand, shore
Template Strand is the DNA strand read by RNA polymerase in the 3-prime to 5-prime direction during transcription, providing the sequence from which a complementary RNA molecule is synthesized.
RNA polymerase moves along the template strand from its 3-prime end toward its 5-prime end, adding ribonucleotides to the growing RNA chain in the 5-prime to 3-prime direction. The resulting RNA sequence is complementary to the template strand and identical in sequence to the non-template strand, except that uracil replaces thymine. At any given gene, either strand of the double helix can serve as the template, depending on the orientation of the gene’s promoter.
In the human genome, roughly equal numbers of genes are transcribed from each strand, and neighboring genes on opposite strands can overlap at their ends.
In bacteria, overlapping genes on opposite DNA strands can share the same nucleotide sequence, with one strand serving as template for one gene while the opposite strand templates a completely different gene. The bacteriophage phiX174 genome, only 5,386 base pairs long, encodes 11 proteins partly through overlapping reading frames on both strands, packing far more information than a simple linear arrangement would allow.
The same DNA strand is always the template for every gene in a genome. Different genes use opposite strands as templates, and the choice is determined by the location and orientation of each gene's promoter.
In human mitochondrial DNA, genes are encoded on both the heavy strand and the light strand. The mitochondrial genome is 16,569 base pairs long, and different transcription units use opposite template strands depending on gene orientation.
Transcription Factor
/ tran-SKRIP-shun FAK-ter / · Latin transcribere (to copy) + Latin factor (maker)
Transcription Factor is a protein that binds specific DNA sequences or other regulatory proteins to activate or repress the transcription of target genes.
Transcription factors typically contain a DNA-binding domain that recognizes specific promoter or enhancer sequences and a transactivation domain that recruits coactivators or the basal transcription machinery. Most are classified as either general factors, which are required at nearly all promoters, or sequence-specific factors, which target defined sets of genes. Combinatorial interactions among sequence-specific factors let a limited number of proteins regulate thousands of genes in a context-dependent manner.
In humans, roughly 1,600 proteins are annotated as transcription factors, yet they collectively govern the expression of the entire genome.
MyoD, a transcription factor discovered in mouse cells in 1987, can redirect certain non-muscle cells toward a muscle-like identity when expressed experimentally. Introducing a single MyoD gene into fibroblasts caused them to activate dozens of muscle-specific genes, demonstrating how one regulatory protein can reprogram a cell's gene expression profile.
Transcription factors are the enzymes that copy DNA into RNA. RNA polymerase carries out that copying reaction, while transcription factors regulate when and how strongly it occurs.
MyoD is a transcription factor that activates muscle-gene programs in vertebrates (including mice, Mus musculus). Experiments introducing the MyoD gene into cultured fibroblasts showed that a single transcription factor can redirect those cells toward a muscle-like identity, activating more than 50 muscle-specific target genes in the process.
Transcription Termination
/ tran-SKRIP-shun ter-mih-NAY-shun / · Latin transcribere, to copy; terminatio, ending
Transcription Termination is the process by which RNA polymerase stops synthesizing RNA and releases the completed transcript from the DNA template.
Without a stopping signal, RNA polymerase would continue copying DNA past the end of a gene and produce aberrant transcripts that interfere with downstream genes. Two main termination mechanisms exist in bacteria. In intrinsic termination, the newly made RNA folds into a stable GC-rich hairpin followed by a run of uracil residues, and this combination causes the polymerase to pause and disengage from the template.
Rho-dependent termination uses a separate protein factor: the Rho helicase tracks along the nascent RNA and unwinds the RNA-DNA hybrid when it catches a stalled polymerase. Eukaryotic RNA polymerase II uses a distinct mechanism in which cleavage of the transcript at a polyadenylation signal, followed by degradation of the downstream RNA by the exonuclease Xrn2, triggers polymerase release.
In the bacterium Escherichia coli, the Rho helicase translocates along nascent RNA at a rate of roughly 55 nucleotides per second to catch a paused polymerase. Rho was first identified by Jeffrey Roberts in 1969 and remains one of the best-characterized termination factors in any organism.
RNA polymerase falls off DNA at random when it runs out of template. Termination depends on specific sequence signals and dedicated molecular machinery that actively dislodge the polymerase at defined endpoints.
Building Blocks of Nucleic Acids →In the bacterium Bacillus subtilis, intrinsic terminators form RNA hairpins of roughly 4 to 8 base pairs followed by a uracil-rich stretch of 7 to 9 residues. These 2 structural features are sufficient to release RNA polymerase without any additional protein factors, and genome-wide studies have identified hundreds of such terminators across the chromosome.
TRNA
/ TEE-ar-en-ay / · Transfer RNA
TRNA is a small non-coding RNA molecule, usually 73 to 93 nucleotides long, that carries a specific amino acid to the ribosome and decodes mRNA codons during translation.
Each tRNA folds into a cloverleaf secondary structure and an L-shaped three-dimensional structure stabilized by modified bases and noncanonical interactions. The 3-prime CCA end carries the amino acid attached by its matching aminoacyl-tRNA synthetase, while the anticodon loop base-pairs with a complementary codon in mRNA. Accurate charging is essential because the ribosome checks codon-anticodon pairing but cannot verify whether the attached amino acid is correct.
Many tRNAs contain modified nucleotides near the anticodon that improve decoding fidelity, stabilize wobble pairing, or prevent frameshifting.
Human cells encode more than 400 nuclear tRNA genes, but many are redundant copies that decode the same codon. This redundancy helps match tRNA abundance to codon usage in highly expressed genes.
Translation Biology →Ribosomes directly read DNA to choose amino acids. Ribosomes read mRNA codons, while tRNA molecules deliver the corresponding amino acids through anticodon-codon pairing.
Building Blocks of Proteins →In Escherichia coli, the initiator tRNA carries formylmethionine and recognizes the AUG start codon at the beginning of bacterial translation. Unlike elongator tRNAs, this initiator tRNA enters directly into the ribosomal P site, one of 3 tRNA-binding sites in the bacterial ribosome.