Molecular Biology Terms Starting With S
Molecular Biology Glossary: S
Sense Strand
/ SENS strand / · Latin sensus, meaning; Old English strand, shore
Sense Strand is the DNA strand that has the same nucleotide sequence as the mRNA transcript, with thymine in place of uracil, and runs 5-prime to 3-prime in the direction of transcription.
During transcription, RNA polymerase reads the antisense strand in the 3-prime to 5-prime direction, synthesizing an mRNA whose sequence matches the sense strand except that uracil replaces thymine at every position. Molecular biologists also call the sense strand the coding strand or non-template strand, while the antisense strand is called the template strand. Confusion between these two strands is a frequent source of error in PCR primer design, because a primer intended to match the mRNA sequence must have the same sequence as the sense strand, not the antisense strand.
Antisense oligonucleotide drugs are designed to be complementary to the sense strand sequence of a target mRNA, allowing them to block translation of disease-causing proteins.
The designation of which strand is "sense" can differ between overlapping genes on the same chromosome. Two genes encoded on opposite strands at the same locus use each other's sense strand as their own antisense strand, a genomic arrangement found at hundreds of loci in the human genome and often associated with regulatory interactions between the two transcripts.
Building Blocks of Nucleic Acids →The sense strand is the strand RNA polymerase reads during transcription. RNA polymerase reads the antisense strand and produces an mRNA that matches the sense strand sequence.
In the human beta-globin gene, the sense strand sequence corresponds to the beta-globin mRNA sequence except for thymine in DNA replacing uracil in RNA. The mature beta-globin coding region encodes a 147-amino-acid protein chain, so reading the sense strand in triplets predicts the amino acid sequence.
Building Blocks of Proteins →Sigma Factor
/ SIG-mah FAK-ter / · Greek sigma, letter sigma; Latin factor, maker
Sigma Factor is a dissociable subunit of bacterial RNA polymerase that confers promoter recognition specificity, directing the core enzyme to bind defined promoter sequences and initiate transcription of a particular set of genes.
Without a sigma factor, the bacterial core RNA polymerase binds DNA nonspecifically and cannot initiate transcription at defined start sites. Sigma subunits contact conserved promoter elements, typically the -10 and -35 hexamers in sigma-70-class promoters, positioning the polymerase precisely over the transcription start site. Different sigma factors recognize different promoter sequences, so bacteria switch on entirely different gene sets by changing which sigma factor is produced or active.
In Escherichia coli, sigma-70 directs transcription of roughly 1,000 housekeeping genes under normal growth conditions, while sigma-32 recognizes heat shock gene promoters and its cellular concentration rises approximately 15-fold within minutes of a temperature shift above 42 degrees Celsius.
Bacillus subtilis encodes 18 sigma factors, more than any other well-studied bacterium. During sporulation, a cascade of four sporulation-specific sigma factors, sigmaF, sigmaE, sigmaG, and sigmaK, are activated in a precise temporal and compartment-specific sequence that coordinates gene expression between the developing spore and the surrounding mother cell.
Bacterial RNA polymerase recognizes every promoter the same way regardless of conditions. Sigma factors guide the core polymerase to specific promoter classes, so the set of genes transcribed changes depending on which sigma factor is present.
Bacillus subtilis activates sigma-B during osmotic stress, heat stress, and ethanol exposure, switching on more than 150 general stress genes within minutes. Strains lacking sigma-B survive acute stress at rates roughly 1,000-fold lower than wild-type cells, demonstrating how a single sigma factor change reshapes the transcriptional output of the cell.
Signal Peptide
/ SIG-nul PEP-tide / · Latin signalis (signal) + Greek peptos (digested)
Signal Peptide is a short amino acid sequence, typically at the N-terminus of a newly synthesized protein, that directs the ribosome-nascent chain complex to the endoplasmic reticulum membrane or targets the protein to another specific cellular compartment.
Signal peptides are usually 16 to 30 amino acids long and contain a central hydrophobic core of 8 to 12 nonpolar residues that is recognized by the signal recognition particle as it emerges from the ribosome. SRP binding pauses translation and docks the ribosome at the translocon channel in the endoplasmic reticulum membrane, where protein synthesis resumes and the growing chain is threaded co-translationally into the ER lumen. Signal peptidase, a protease located on the luminal face of the ER membrane, cleaves the signal peptide from the mature protein shortly after translocation begins.
Proteins lacking a functional signal peptide are synthesized on free ribosomes in the cytosol and remain there unless they carry a different targeting sequence directing them elsewhere.
Mitochondria and chloroplasts use their own distinct targeting sequences, called transit peptides, rather than signal peptides recognized by the SRP pathway. Transit peptides are recognized by protein import complexes in the outer and inner membranes of these organelles, and unlike signal peptides they are imported post-translationally after the protein is fully synthesized in the cytosol.
Signal peptides are permanent parts of the mature protein. Signal peptidase cleaves the signal peptide from the protein shortly after translocation into the ER lumen, so the mature secreted or membrane protein retains no signal peptide sequence.
Preproinsulin, synthesized in pancreatic beta cells, carries a 24-amino-acid signal peptide that directs it into the ER lumen within seconds of synthesis beginning. Once inside the ER, signal peptidase removes those 24 residues, converting preproinsulin to proinsulin, which then folds and undergoes further processing in the Golgi apparatus.
Signal Recognition Particle
/ SIG-nul rek-ug-NISH-un PAR-tih-kul / · Scientific term used in protein trafficking.
Signal Recognition Particle is a ribonucleoprotein complex that recognizes the signal peptide emerging from a translating ribosome, transiently pauses translation, and delivers the ribosome-nascent chain complex to the SRP receptor on the endoplasmic reticulum membrane.
In mammals, the SRP is composed of a 7S RNA scaffold and six protein subunits designated SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72. The SRP54 subunit contains the methionine-rich M domain that directly contacts the hydrophobic core of the signal peptide as it exits the ribosome tunnel. GTP binding by both SRP54 and the SRP receptor drives docking of the ribosome at the translocon, and GTP hydrolysis releases SRP so it can return to the cytosol for another round of targeting.
Without functional SRP, signal-peptide-bearing proteins are synthesized on cytosolic ribosomes and either misfold or are degraded, disrupting the secretory pathway.
The core mechanism of SRP-mediated targeting is conserved from bacteria to humans, but the bacterial SRP is far simpler, consisting of a single protein called Ffh and a small 4.5S RNA. Structural studies published in 2004 by the Stroud and Walter laboratories showed that the bacterial and mammalian SRP54 and Ffh proteins adopt nearly identical three-dimensional folds despite sharing less than 25 percent amino acid sequence identity.
Translation Biology →Secreted proteins finish translation in the cytosol before finding the endoplasmic reticulum. SRP captures the signal peptide while the protein is still being synthesized, coupling translation and translocation so the protein enters the ER co-translationally.
In the nematode Caenorhabditis elegans, loss-of-function mutations in the gene encoding the SRP54 homolog cause embryonic lethality because secreted and membrane proteins cannot reach the ER. Roughly 30 percent of all proteins encoded in the C. elegans genome are predicted to enter the secretory pathway, illustrating how broadly the SRP targeting system is used across the proteome.
Silencer
/ SY-len-ser / · Latin silere, to be silent; -er, agent suffix
Silencer is a cis-acting DNA regulatory element that reduces transcription of a gene when bound by repressor proteins or repressive chromatin complexes.
Silencers can function near a promoter or at long distances through chromatin looping, much like enhancers, but they recruit molecular machinery that lowers transcription rather than increasing it. Repressor proteins bound at silencers can block activator binding, recruit histone deacetylases, promote Polycomb-mediated H3K27me3 deposition, or stabilize compact chromatin. Silencers are essential for cell identity because they keep neuronal, muscle, immune, or developmental genes inactive in cell types where those programs would be inappropriate.
Loss of silencer function can activate normally restricted genes in cancer, developmental disorders, and immune dysregulation.
The neuron-restrictive silencer element is bound by REST, a repressor that controls more than 2,000 neuronal genes in non-neuronal cells. Removing REST activity can derepress neuronal gene networks in cells that normally never express them.
All regulatory DNA increases gene expression. Silencers are regulatory elements that lower or shut off transcription by recruiting repressors or repressive chromatin machinery.
REST binds neuron-restrictive silencer elements near genes encoding ion channels, synaptic proteins, and neurotransmitter receptors. In non-neuronal human cells, REST occupancy can reduce transcription of target genes by more than 10-fold, helping prevent inappropriate neuronal gene expression.
Small Interfering RNA
/ SMAWL IN-ter-FEER-ing R-N-A / · English small + Latin interferere (to interfere)
Small Interfering RNA is a short double-stranded RNA molecule, usually about 21 nucleotides long, that guides Argonaute-containing silencing complexes to complementary RNA targets.
Small interfering RNAs arise when Dicer processes long double-stranded RNA into short duplexes with characteristic 2-nucleotide 3-prime overhangs. One strand is loaded into RISC as the guide strand, while the passenger strand is discarded. If the guide matches a target mRNA with near-perfect complementarity, AGO2 cleaves the mRNA and promotes its degradation.
Synthetic siRNAs are widely used for gene knockdown in research, and RNAi therapeutics use chemical modifications and delivery systems such as lipid nanoparticles or GalNAc conjugates to target disease-related transcripts in patients.
Patisiran became the first FDA-approved RNAi therapeutic in 2018. It uses lipid nanoparticles to deliver siRNA to liver cells and reduce transthyretin production in hereditary transthyretin-mediated amyloidosis.
siRNA works by cutting DNA. siRNA guides protein complexes to matching RNA molecules, causing RNA cleavage or repression while leaving genomic DNA unchanged.
Building Blocks of Nucleic Acids →In Caenorhabditis elegans, feeding worms bacteria engineered to produce double-stranded RNA can silence matching genes throughout the animal. A single feeding experiment can reduce target gene expression by more than 90 percent within 24 hours.
Southern Blotting
/ SUH-thern BLOT-ing / · Named after inventor Edwin Southern (1975)
Southern Blotting is a laboratory method that detects specific DNA fragments by electrophoretic separation, membrane transfer, and hybridization with a labeled complementary probe.
The method begins by digesting genomic DNA with restriction enzymes, separating the fragments by agarose gel electrophoresis, and denaturing the DNA so that single strands can bind a probe. After electrophoresis, fragments are transferred to a nylon or nitrocellulose membrane, where a labeled DNA probe hybridizes only to complementary sequences. Band size reveals the length of the restriction fragment carrying the target sequence, while band intensity can provide semi-quantitative information about copy number.
Although PCR and sequencing have replaced Southern blotting for many applications, it remains useful for detecting large insertions, repeat expansions, transgene integration patterns, and structural rearrangements that short-read methods may miss.
Southern blotting was developed by Edwin Southern in 1975, and the later names Northern and Western blotting were jokes based on his surname. The method helped establish modern DNA diagnostics before PCR became routine.
Southern blotting detects RNA because Northern blotting sounds similar. Southern blotting detects DNA, Northern blotting detects RNA, and Western blotting detects proteins.
Building Blocks of Nucleic Acids →Early forensic DNA profiling used Southern blotting to compare variable-number tandem repeat patterns between suspects and crime-scene samples. A single VNTR probe could produce multiple bands ranging from 1 to more than 20 kilobases, creating a pattern distinctive enough for identity testing before STR-PCR replaced the method.
Spliceosome
/ SPLIE-see-oh-sohm / · Greek splicein (to splice) + Latin soma (body)
Spliceosome is a large ribonucleoprotein machine that removes introns from pre-mRNA and joins adjacent exons to produce mature mRNA.
The major spliceosome contains five small nuclear ribonucleoproteins, U1, U2, U4, U5, and U6, plus more than 150 associated proteins that assemble stepwise on each intron. U1 recognizes the 5-prime splice site, U2 binds the branch point, and rearrangements among U2, U5, and U6 create the catalytic center that carries out two transesterification reactions. The intron is released as a lariat, while the flanking exons are ligated into a continuous coding sequence.
A separate minor spliceosome processes a rare class of U12-type introns, showing that eukaryotic cells maintain two related but distinct splicing machines.
The catalytic heart of the spliceosome is RNA-rich rather than purely protein-based. U2 and U6 small nuclear RNAs form much of the active site, placing the spliceosome among the major ribonucleoprotein catalysts in modern cells.
Splicing is performed by one simple protein. The spliceosome contains five small nuclear RNAs and more than 150 proteins that assemble, rearrange, and disassemble for each intron.
Human U1 small nuclear RNA base-pairs with the 5-prime splice site during the earliest spliceosome assembly step. A mismatch affecting even 1 of the conserved splice-site nucleotides can shift splice-site choice and produce aberrant mRNA isoforms in disease genes.
Splicing
/ SPLIE-sing / · Old High German: spaltan (to split)
Splicing is the RNA processing reaction that removes introns from a pre-mRNA transcript and joins the remaining exons into a mature mRNA.
Splicing occurs through two transesterification reactions catalyzed by the spliceosome. First, the branch point adenosine attacks the 5-prime splice site, forming a lariat intermediate; second, the free 3-prime hydroxyl of the upstream exon attacks the 3-prime splice site, ligating the two exons. Splicing must be highly accurate because even a single-nucleotide shift can alter the reading frame or introduce a premature stop codon.
Alternative splicing expands proteome diversity by allowing different exon combinations to be included in different tissues, developmental stages, or signaling states.
Splicing errors are a major cause of inherited disease. Analyses of disease-mutation databases estimate that roughly 15 percent of pathogenic point mutations disrupt splice sites or splicing regulatory sequences.
All RNA copied from a gene is translated directly. Many eukaryotic transcripts must be spliced, capped, and polyadenylated before they become export-competent mature mRNAs.
Beta-globin pre-mRNA undergoes splicing to remove 2 introns before translation. Mutations at HBB splice sites can reduce correctly spliced beta-globin mRNA by more than 50 percent in severe alleles, lowering hemoglobin production and causing beta-thalassemia.
Stem-Loop Structure
/ STEM LOOP STRUK-chur / · Old English stemm (support) + Old English hlyp (leap)
Stem-Loop Structure is an RNA or single-stranded DNA secondary structure formed when complementary sequences within the same strand base-pair to create a double-stranded stem capped by an unpaired loop.
Stem-loops form when inverted repeat sequences within a strand anneal to one another through Watson-Crick and wobble base pairing. Their stability depends on stem length, GC content, loop size, salt concentration, and competing interactions with proteins or other RNA regions. In bacteria, GC-rich stem-loops followed by uridine tracts can function as intrinsic transcription terminators.
Eukaryotic stem-loops shape microRNA precursors, regulate mRNA stability, and provide binding sites for RNA-binding proteins that control translation or localization.
The iron-responsive element is a stem-loop in ferritin mRNA that controls iron storage. When iron is scarce, iron regulatory proteins bind this structure and block translation, preventing the cell from making unnecessary ferritin.
Single-stranded RNA has no stable structure. Many RNAs fold into stem-loops, bulges, pseudoknots, and long-range interactions that are essential for their biological activity.
Bacterial intrinsic terminators contain a GC-rich stem-loop followed by a run of uridine residues in the nascent RNA. A typical terminator stem contains 7 to 20 base pairs, enough to pause RNA polymerase and destabilize the RNA-DNA hybrid.