Page last updated: 2024-10-24

negative regulation of primary miRNA processing

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of primary microRNA processing. [GOC:dph, GOC:sl]

Negative regulation of primary miRNA processing involves a complex interplay of factors that modulate the production of mature miRNAs. These miRNAs play crucial roles in gene regulation, influencing a wide range of cellular processes. The process begins with the transcription of a primary miRNA (pri-miRNA) transcript by RNA polymerase II. This pri-miRNA is a long RNA molecule containing the hairpin structure that will eventually give rise to the mature miRNA. The first step in negative regulation is the inhibition of pri-miRNA transcription. This can be achieved by various mechanisms, including:
* **Repression of the miRNA gene promoter:** Transcription factors can bind to the promoter region of the miRNA gene, blocking the recruitment of RNA polymerase II and preventing transcription.
* **Chromatin modifications:** Modifications like methylation and acetylation of histones in the chromatin surrounding the miRNA gene can affect its accessibility to transcription machinery.
* **RNA polymerase II inhibition:** Factors that directly inhibit the activity of RNA polymerase II can also reduce pri-miRNA transcription.

Once a pri-miRNA transcript is produced, its processing can be further regulated. Several key players are involved in this step:
* **Drosha-DGCR8 complex:** This complex is responsible for cleaving the pri-miRNA in the nucleus, generating a shorter precursor miRNA (pre-miRNA) hairpin.
* **Exportin-5:** This protein escorts the pre-miRNA from the nucleus to the cytoplasm.
* **Dicer:** This enzyme cleaves the pre-miRNA in the cytoplasm, generating a mature miRNA duplex.
* **RISC complex:** The mature miRNA duplex is loaded into the RISC complex, where one strand is incorporated and the other is degraded.

Negative regulation can occur at each of these processing steps:
* **Drosha-DGCR8 inhibition:** Certain proteins can interact with the Drosha-DGCR8 complex, inhibiting its activity and reducing the production of pre-miRNA.
* **Exportin-5 inhibition:** Factors that block the export of pre-miRNAs from the nucleus can hinder their processing into mature miRNAs.
* **Dicer inhibition:** Proteins that bind to Dicer or interfere with its catalytic activity can inhibit the cleavage of pre-miRNAs.
* **RISC loading inhibition:** Factors that prevent the proper loading of mature miRNAs into the RISC complex can disrupt the downstream silencing functions of the miRNA.

The negative regulation of primary miRNA processing is essential for maintaining proper cellular homeostasis. Dysregulation of this process can lead to aberrant miRNA expression and contribute to various diseases, including cancer and developmental disorders. Understanding the mechanisms involved in this regulation is crucial for developing therapeutic strategies targeting miRNA pathways.'
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Proteins (2)

ProteinDefinitionTaxonomy
Signal transducer and activator of transcription 3A signal transducer and activator of transcription 3 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P40763]Homo sapiens (human)
Interleukin-6An interleukin-6 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P05231]Homo sapiens (human)

Compounds (30)

CompoundDefinitionClassesRoles
niclosamideniclosamide : A secondary carboxamide resulting from the formal condensation of the carboxy group of 5-chlorosalicylic acid with the amino group of 2-chloro-4-nitroaniline. It is an oral anthelmintic drug approved for use against tapeworm infections.

Niclosamide: An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48)
benzamides;
C-nitro compound;
monochlorobenzenes;
salicylanilides;
secondary carboxamide
anthelminthic drug;
anticoronaviral agent;
antiparasitic agent;
apoptosis inducer;
molluscicide;
piscicide;
STAT3 inhibitor
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
nitazoxanidenitazoxanide: a 5-nitrothiazolyl derivative used for a broad range of intestinal parasitic infections including CRYPTOSPORIDIUM and GIARDIA; it is a redox-active nitrothiazolyl-salicylamide prodrugbenzamides;
carboxylic ester
bergeninbergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structuretrihydroxybenzoic acidmetabolite
loganinbeta-D-glucoside;
cyclopentapyran;
enoate ester;
iridoid monoterpenoid;
methyl ester;
monosaccharide derivative;
secondary alcohol
anti-inflammatory agent;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
EC 3.4.23.46 (memapsin 2) inhibitor;
neuroprotective agent;
plant metabolite
tetrahydrocurcumintetrahydrocurcumin : A beta-diketone that is curcumin in which both of the double bonds have been reduced to single bonds.beta-diketone;
diarylheptanoid;
polyphenol
metabolite
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
ar-turmerone(+)-(S)-ar-turmerone : A sesquiterpenoid that is 2-methylhept-2-en-4-one substituted by a 4-methylphenyl group at position 6. It has been isolated from Peltophorum dasyrachis.

ar-turmerone: potent antivenom against snake bites; isolated form Curcuma longa; structure given in first source
enone;
sesquiterpenoid
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
plant metabolite
swerosideglycoside
nsc 74859NSC 74859: inhibits Stat3 binding activity; structure in first source

S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid.
amidobenzoic acid;
monohydroxybenzoic acid;
tosylate ester
STAT3 inhibitor
telocinobufagintelocinobufagin: structuresteroid lactone
tizoxanidetizoxanide: major metabolite of nitazoxanide; structure in first sourcesalicylamides
bardoxolone methylmethyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate: structure in first sourcecyclohexenones
bisabololKamillosan: drug combination containing chamomile and bisabolol; used to treat dermatitissesquiterpenoid
ganoderic acid atriterpenoid
piplartinepiplartine: Antineoplastic Agent, Phytogenic; alkaloid from Piper; structure in first sourcecinnamamides;
dicarboximide
stattic1-benzothiophenes;
C-nitro compound;
sulfone
antineoplastic agent;
radiosensitizing agent;
STAT3 inhibitor
stx-0119STX-0119: antineoplastic; structure in first source
genistein7-hydroxyisoflavonesantineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
human urinary metabolite;
phytoestrogen;
plant metabolite;
tyrosine kinase inhibitor
andrographolidecarbobicyclic compound;
gamma-lactone;
labdane diterpenoid;
primary alcohol;
secondary alcohol
anti-HIV agent;
anti-inflammatory drug;
antineoplastic agent;
metabolite
nifuroxazidenifuroxazide: structurebenzoic acids
hylin
2-acetylfuranonaphthoquinone2-acetylfuranonaphthoquinone: has antineoplastic activity; structure in first source
5,15-diphenylporphine5,15-diphenylporphine: structure in first source
wp1066
azd 1480
bi 653048 bs h3po4BI 653048 BS H3PO4: structure in first source
bp-1-102BP-1-102: a STAT3 inhibitor; structure in first source
phaeosphaeride aphaeosphaeride A: inhibits STAT3-dependent signaling; structure in first source
hydrazinocurcuminhydrazinocurcumin : A pyrazole obtained by cyclocodensation of the two carbonyl groups of curcumin with hydrazine.

hydrazinocurcumin: structure in first source
aromatic ether;
olefinic compound;
polyphenol;
pyrazoles
angiogenesis modulating agent;
antineoplastic agent;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor