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ribosomal protein import into nucleus

Definition

Target type: biologicalprocess

The directed movement of a ribosomal protein from the cytoplasm into the nucleus, across the nuclear membrane. At least some ribosomal proteins, including rpl12, uses the importin 11 pathway as a major route into the nucleus. [GOC:ai, PMID:11809816]

Ribosomal proteins (RPs) are essential components of ribosomes, the cellular machinery responsible for protein synthesis. While ribosomes primarily function in the cytoplasm, the assembly of ribosomal subunits occurs in the nucleolus. This necessitates the import of RPs from the cytoplasm into the nucleus. The process of RP import is a complex and tightly regulated mechanism involving a specialized machinery and multiple steps:

1. **RP Recognition and Binding:** RPs, typically synthesized in the cytoplasm, are recognized by import receptors. These receptors are nuclear transport factors that bind specifically to the N-terminal extension (NTE) of RPs. This NTE is a short, unstructured region that is essential for import and often contains a nuclear localization signal (NLS) that targets the RP to the nucleus.

2. **Nuclear Pore Complex Translocation:** Once bound to the import receptor, the RP-receptor complex is transported to the nuclear pore complex (NPC), the gatekeeper of the nucleus. The NPC is a large, multi-protein complex that spans the nuclear envelope. It allows selective passage of molecules between the cytoplasm and the nucleus.

3. **Importin α/β Interactions:** The import receptor often interacts with a second nuclear transport factor called importin β. Importin β is responsible for interacting with the NPC and facilitating the passage of the RP-receptor complex through the pore.

4. **Nuclear Release and Recycling:** Once inside the nucleus, the RP is released from the import receptor. This release is triggered by RanGTP, a small GTPase that is specifically enriched in the nucleus. RanGTP binds to the import receptor, causing a conformational change that weakens the interaction between the receptor and the RP. The import receptor, now bound to RanGTP, is then transported back to the cytoplasm, where it can be recycled for another round of import.

5. **Nucleolar Localization:** After being released from the import receptor, RPs are targeted to the nucleolus, the site of ribosome subunit assembly. The nucleolus is a specialized region within the nucleus where ribosomal RNA (rRNA) synthesis and ribosome assembly occur. RPs bind to rRNA and other ribosomal proteins, leading to the formation of pre-ribosomal particles.

6. **Ribosome Assembly:** In the nucleolus, pre-ribosomal particles undergo a series of maturation steps involving modifications, processing, and assembly of various ribosomal components. Ultimately, these particles are exported from the nucleus to the cytoplasm, where they become functional ribosomes ready to participate in protein synthesis.

The process of RP import into the nucleus is a crucial step in ensuring the proper function of ribosomes and protein synthesis. This process is tightly regulated by a complex network of factors and interactions, ensuring that RPs are transported efficiently and specifically to the nucleolus, where they can contribute to the formation of new ribosomes.'
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Proteins (1)

ProteinDefinitionTaxonomy
60S ribosomal protein L23A eukaryotic-type large ribosomal subunit protein uL14 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62829]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
gentamicin sulfate
PF-06446846PF-06446846 : A triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9.

PF-06446846: inhibits translation of PCSK9 ;structure in first source
benzamides;
monochloropyridine;
piperidines;
tertiary carboxamide;
triazolopyridine
antilipemic drug;
EC 3.4.21.61 (kexin) inhibitor