Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase I. [GOC:go_curators]
Negative regulation of transcription by RNA polymerase I is a complex process involving a variety of factors that act to suppress the production of ribosomal RNA (rRNA). rRNA is a key component of ribosomes, the cellular machinery responsible for protein synthesis. Therefore, regulating its production is essential for maintaining cellular homeostasis.
One of the primary mechanisms of negative regulation involves the binding of repressor proteins to specific DNA sequences within the rRNA gene promoter. These repressors can block the binding of transcription factors required for RNA polymerase I recruitment and initiation of transcription. Examples of such repressors include:
* **Upstream Binding Factor (UBF):** UBF is a key transcription factor for rRNA gene transcription, but its interaction with the promoter can be inhibited by other factors. For instance, the nucleolar protein **Nopp140** can bind to UBF and prevent it from activating transcription.
* **TIF-IA:** TIF-IA is another transcription factor essential for RNA polymerase I activity. Its activity is regulated by proteins like **SL1** (also known as TBP-associated factor 1), which can interact with TIF-IA and inhibit its function.
* **Other Repressors:** Additional repressors, such as **rRNA transcription termination factor 1 (TTF-1)** and **p53**, can also contribute to the negative regulation of RNA polymerase I transcription by blocking the initiation of transcription or promoting premature termination of transcription.
**Post-transcriptional regulation:** Beyond the transcriptional level, the production of rRNA can be controlled by mechanisms affecting the processing and stability of rRNA transcripts.
* **Ribosomal protein availability:** The availability of ribosomal proteins is critical for rRNA processing and ribosome assembly. When ribosomal protein levels are low, the production of rRNA may be reduced.
* **Nucleolar stress:** Stressful conditions, such as DNA damage or nutrient deprivation, can trigger a response that leads to the inhibition of rRNA synthesis. This can involve the phosphorylation and inactivation of transcription factors or the induction of specific microRNAs that target rRNA transcripts.
In summary, the negative regulation of transcription by RNA polymerase I involves a diverse array of mechanisms that ensure proper control of rRNA production. These mechanisms are tightly regulated and can be influenced by various cellular signals and stressors, ultimately contributing to the overall balance and function of the cell.'
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Protein | Definition | Taxonomy |
---|---|---|
Bromodomain adjacent to zinc finger domain protein 2A | A bromodomain adjacent to zinc finger domain protein 2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UIF9] | Homo sapiens (human) |
CREB-binding protein | A CREB-binding protein that is encoded in the genome of human. [PMID:11331617] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
altretamine | Altretamine: A hexamethyl-2,4,6-triamine derivative of 1,3,5-triazine. | triamino-1,3,5-triazine | |
cgs 15943 | 9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine: non-xanthine triazoloquinazoline adenosine antagonist CGS 15943 : A member of the class of triazoloquinazolines that is [1,2,4]triazolo[1,5-c]quinazoline substited at positions 2, 5 and 9 by furan-2-yl, amino and chloro groups respectively. A potent antagonist at adenosine A1 and adenosine A2A receptors. | aromatic amine; biaryl; furans; organochlorine compound; primary amino compound; quinazolines; triazoloquinazoline | adenosine A1 receptor antagonist; adenosine A2A receptor antagonist; antineoplastic agent; central nervous system stimulant |
etazolate | etazolate : A pyrazolopyridine that is 1H-pyrazolo[3,4-b]pyridine which is substituted at positions 1, 4, and 5 by ethyl, 2-isopropylidenehydrazino, and ethoxycarbonyl groups, respectively. A phosphodiesterase IV inhibitor with antidepressant and anxiolytic properties. Etazolate: A potent phosphodiesterase inhibitor proposed as an antipsychotic agent. | ethyl ester; hydrazone; pyrazolopyridine | alpha-secretase activator; antidepressant; antipsychotic agent; anxiolytic drug; GABA agent; neuroprotective agent; phosphodiesterase IV inhibitor |
nocodazole | aromatic ketone; benzimidazoles; carbamate ester; thiophenes | antimitotic; antineoplastic agent; microtubule-destabilising agent; tubulin modulator | |
papaverine | papaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum. Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. | benzylisoquinoline alkaloid; dimethoxybenzene; isoquinolines | antispasmodic drug; vasodilator agent |
ici 136,753 | pyrazolopyridine | ||
3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole | 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole: antineoplastic; activates platelet guanylate cyclase; a radiosensitizing agent and guanylate cyclase activator; structure in first source lificiguat : A member of the class of indazoles that is 1H-indazole which is substituted by a benzyl group at position 1 and a 5-(hydroxymethyl)-2-furyl group at position 3. It is an activator of soluble guanylate cyclase and inhibits platelet aggregation. | aromatic primary alcohol; furans; indazoles | antineoplastic agent; apoptosis inducer; platelet aggregation inhibitor; soluble guanylate cyclase activator; vasodilator agent |
colchicine | (S)-colchicine : A colchicine that has (S)-configuration. It is a secondary metabolite, has anti-inflammatory properties and is used to treat gout, crystal-induced joint inflammation, familial Mediterranean fever, and many other conditions. | alkaloid; colchicine | anti-inflammatory agent; gout suppressant; mutagen |
n-methylpyrrolidone | 1-methylpyrrolidin-2-one: structure in first source N-methylpyrrolidin-2-one : A member of the class of pyrrolidine-2-ones that is pyrrolidin-2-one in which the hydrogen attached to the nitrogen is replaced by a methyl group. | lactam; N-alkylpyrrolidine; pyrrolidin-2-ones | polar aprotic solvent |
4-Methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one | benzodiazepine | ||
epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
delphinidin | delphinidin chloride : An anthocyanidin chloride that has delphinidin as the cationic counterpart. Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical anti-inflammatory. It is also commonly used as an embedding material in histology. | anthocyanidin chloride | |
oxoglaucine | 1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one: a phosphatidylinositol 3-kinase p110alpha inhibitor that reactivates latent HIV-1; structure in first source | isoquinoline alkaloid | |
mrs 1220 | 9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline: structure in first source | quinazolines | |
rolipram | (-)-rolipram : The (R)-enantiomer of rolipram. | rolipram | |
2-methyl-2,3,4,5-tetrahydro-1,5-benzoxazepin-4-one | organonitrogen heterocyclic compound; oxacycle | ||
methyl indole-3-carboxylate | methyl indole-3-carboxylate : The methyl ester of indole-3-carboxylic acid. | indoles; methyl ester | metabolite |
4-(1H-benzimidazol-2-ylmethylthio)-2-methylbenzofuro[3,2-d]pyrimidine | benzimidazoles | ||
2-(4-benzofuro[3,2-d]pyrimidinylthio)-1-thiophen-2-ylethanone | benzofurans | ||
curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
4-[2-(9-methyl-6-indolo[3,2-b]quinoxalinyl)ethyl]morpholine | quinoxaline derivative | ||
N-[4,6-bis(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(methylthio)-1,3-benzothiazol-6-amine | benzothiazoles | ||
fisetin | 3'-hydroxyflavonoid; 7-hydroxyflavonol; tetrahydroxyflavone | anti-inflammatory agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; metabolite; plant metabolite | |
icg 001 | peptide | ||
jq1 compound | carboxylic ester; organochlorine compound; tert-butyl ester; thienotriazolodiazepine | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; bromodomain-containing protein 4 inhibitor; cardioprotective agent; ferroptosis inducer | |
gsk525762a | molibresib: mimicks acetylated histones; structure in first source | benzodiazepine | |
gsk1210151a | GSK1210151A: inhibitor of the BET family of proteins; structure in first source | imidazoquinoline | |
i-bet726 | |||
2-methoxy-n-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide | 2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide: a probe for bromo and extra C-terminal domain proteins; structure in first source | quinazolines | |
rvx 208 | apabetalone: a bromodomain and extra-terminal domain protein (BET) inhibitor; prevents interactions between BET proteins and acetyl-lysine residues on histone tails to modify epigenetic regulation |