rescue of stalled ribosome

Definition

Target type: biologicalprocess

A process of translational elongation that takes place when a ribosome has stalled during translation, and results in freeing the ribosome from the stalled translation complex. [GOC:jh2, GOC:mah, PMID:18557701, PMID:19170872, PMID:20117091, PMID:20185543]

Ribosome stalling is a common occurrence during protein synthesis, often triggered by factors such as mRNA secondary structures, codon scarcity, or the presence of damaged or misfolded proteins. When a ribosome stalls, it can block the translation of downstream mRNA and disrupt cellular homeostasis. To prevent these disruptions, cells have evolved intricate mechanisms to rescue stalled ribosomes. These mechanisms involve a complex interplay of proteins, RNA, and cellular pathways.

One prominent rescue pathway is the **translational bypass pathway** that allows ribosomes to skip over problematic sequences and continue translation. This pathway often involves specialized translation factors, such as **ribosome rescue factors (RRFs)**, which bind to the A site of the ribosome and promote the release of the stalled tRNA. These factors also facilitate the recruitment of other proteins, such as **elongation factors (EFs)**, which help to reposition the ribosome and allow translation to resume.

Another essential pathway involves the **endonuclease-mediated mRNA cleavage pathway**. This pathway uses specialized enzymes, such as **Pelota** and **Hbs1**, to cleave the mRNA downstream of the stalled ribosome. This cleavage event removes the problematic sequence and allows the ribosome to dissociate from the mRNA. Importantly, the cleaved mRNA can be re-translated, preventing a complete loss of protein production.

Additionally, the **ubiquitin-proteasome system** plays a crucial role in ribosome rescue. This system targets stalled ribosomes and their associated mRNA for degradation by proteasomes. This process ensures the removal of unproductive ribosomes and prevents their accumulation, which can disrupt cellular function.

The **ribosomal quality control (RQC)** system represents another crucial component of ribosome rescue. This system monitors the quality of translation products and employs mechanisms to degrade aberrant or incomplete proteins. RQC pathways rely on specific E3 ligases that ubiquitinate stalled ribosomes, marking them for degradation by proteasomes.

Finally, some ribosome rescue pathways are specifically designed to address particular types of ribosome stalling. For example, the **non-stop decay (NSD)** pathway targets ribosomes that have stalled due to a lack of stop codon. This pathway uses a specialized factor called **SsrA**, which binds to the A site of the stalled ribosome and recruits other factors to degrade the incomplete protein and the associated mRNA.

Overall, the rescue of stalled ribosomes is a multifaceted process that involves diverse cellular mechanisms. These mechanisms are essential for maintaining protein synthesis fidelity, preventing disruptions in cellular function, and ensuring cellular homeostasis.'
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Proteins (1)

Compounds (1)