RNA polymerase, promoters, elongation, splicing, capping, polyadenylation, ncRNA biogenesis.
Transcription
Transcription
Template-directed synthesis of RNA from DNA by RNA polymerase. Initiation (promoter recognition), elongation (NTP addition 5′→3′),…
RNA polymerase II
Eukaryotic 12-subunit polymerase synthesising all mRNA and most snRNA/miRNA. CTD heptad repeats on Rpb1 phosphorylated serially at Ser5…
Promoter
DNA sequence upstream of a gene that recruits RNA polymerase. Eukaryotic core promoter (TATA box, Inr, DPE) binds general transcription…
General transcription factor (GTF)
Basal machinery that positions pol II at core promoter: TFIIA/B/D/E/F/H assemble sequentially. TFIID contains TBP (TATA-binding protein) +…
Enhancer
Distal regulatory DNA element (100-1000 bp) that activates transcription in a cell-type- or signal-specific manner, orientation/position…
Pre-mRNA splicing
Removal of introns and ligation of exons by the spliceosome (U1/U2/U4/U5/U6 snRNPs + proteins, ~200 components). Two-step…
5′-capping
Co-transcriptional addition of 7-methylguanosine cap via 5′-5′ triphosphate bridge to nascent mRNA. Essential for stability, export, and…
Polyadenylation
Endonucleolytic cleavage at poly(A) signal (AAUAAA) + addition of ~200 A residues by poly(A) polymerase. Stabilises mRNA, promotes export,…
microRNA (miRNA)
~22-nt non-coding RNAs processed from hairpin precursors by Drosha + Dicer; guide RISC (Argonaute) to target mRNA 3′ UTR for translational…
Long non-coding RNA (lncRNA)
RNA >200 nt without coding potential. Functions: chromatin scaffolding (XIST, HOTAIR), enhancer RNAs, nuclear compartment organisation…
RNA polymerase elongation kinetics framework
Eukaryotic RNA Pol II elongates pre-mRNA at ~1-4 kb/min (single-molecule). Pause-and-restart kinetics: backtracking → arrest, rescued by…
Transcription-factor cooperativity / enhancer framework
Enhancers: ~1-10 kb DNA modules binding 4-12 transcription factors that cooperatively assemble (Hill coefficient n_H ≈ 2-5) and activate…
Operon (Jacob-Monod 1961)
Jacob-Monod 1961 (Nobel 1965) lac-operon + repressor; modern lac/trp/ara prokaryote-paradigms.
Eukaryotic Pol I/II/III (Roeder 1969)
R Roeder 1969 RNA-pol I/II/III in eukaryotes; modern Cramer 2000 atomic-structure RNAP-II.
Transcription factor
Crawford 1979 + Ptashne 1986 'Genetic Switch' lambda-cI; modern Vaquerizas 2009 ~1500 human-TFs catalogued.
Enhancer-promoter (Banerji-Schaffner 1981)
Banerji-Schaffner 1981 enhancer-discovery; modern Mediator-complex + cohesin-loop + Hi-C topology Lieberman-Aiden 2009.
Alternative splicing (Modrek-Lee 2002)
Modrek-Lee 2002 + Wang 2008 95% multi-exon human genes alt-spliced; modern Splice-AI + machine-learning.
Transcriptional bursting (Suter 2011)
Suter-Naef 2011 transcriptional-bursting in mammalian cells; modern smFISH + scRNA-seq across species.
Pol I/II/III (Roeder-Rutter 1969)
R Roeder-W Rutter 1969 RNA-polymerase I/II/III; modern modern foundational text + structural Cramer 2001 + Kornberg Nobel 2006.
Pol II structure (Kornberg 2001)
R Kornberg 2001 (Nobel 2006) Pol-II crystal structure; modern modern Cramer + cryo-EM elongation + termination + Mediator.
TATA box (Goldberg 1979)
M Goldberg 1979 + Hogness Goldberg-Hogness box; modern foundational core-promoter + TFIID + TBP + 2024 EnhancerAtlas 2.0.
Histone code (Allis 2001)
C D Allis-T Jenuwein 2001 histone-code; modern epigenetic-marks H3K4 / H3K27 / H3K9 + writers / readers / erasers druggable.
ChIP-seq (Mikkelsen 2007)
T Mikkelsen-B Bernstein 2007 + Robertson 2007 ChIP-seq; modern Cut&Run / Cut&Tag-Henikoff + low-input + 2024 single-cell 10x.
LLPS (Hyman 2014)
A Hyman-C Brangwynne 2014 + Eisen 2018 phase-sep + transcription-condensate; modern modern 2024 super-enhancer + RNA-protein gels.