deadenylation-dependent decapping of nuclear-transcribed mRNA

Definition

Target type: biologicalprocess

Cleavage of the 5'-cap of a nuclear mRNA triggered by shortening of the poly(A) tail to below a minimum functional length. [GOC:krc]

Deadenylation-dependent decapping of nuclear-transcribed mRNA is a crucial step in the degradation of eukaryotic messenger RNA (mRNA) and plays a vital role in regulating gene expression. It involves a tightly regulated cascade of events that starts with the shortening of the poly(A) tail at the 3' end of the mRNA molecule and culminates in the removal of the 5' cap structure. This process is particularly important for nuclear-transcribed mRNAs, which are synthesized in the nucleus and then exported to the cytoplasm for translation. Here's a detailed description of the key steps involved:

1. **Deadenylation:** The first step in this pathway is the removal of adenine nucleotides from the poly(A) tail at the 3' end of the mRNA. This process is catalyzed by a group of enzymes known as deadenylases, which shorten the poly(A) tail gradually. As the poly(A) tail becomes shorter, the mRNA becomes progressively less stable and more susceptible to degradation.

2. **Decapping:** Once the poly(A) tail has been sufficiently shortened, the 5' cap structure, which is a 7-methylguanosine residue linked to the first nucleotide of the mRNA, is removed by the decapping enzyme complex. This complex consists of several proteins, including Dcp1 and Dcp2. The removal of the 5' cap exposes the mRNA to exonucleases, which can degrade the mRNA from the 5' end.

3. **5'-3' Exonucleolytic Degradation:** After decapping, the mRNA becomes vulnerable to degradation by 5'-3' exonucleases. These enzymes degrade the mRNA molecule from the 5' end towards the 3' end, breaking down the mRNA into individual nucleotides.

4. **3'-5' Exonucleolytic Degradation:** In some cases, the mRNA may also be degraded by 3'-5' exonucleases, which degrade the mRNA from the 3' end towards the 5' end. This degradation pathway is less common than 5'-3' exonucleolytic degradation.

5. **Exosome-Mediated Degradation:** The exosome, a multi-protein complex, can also contribute to mRNA degradation. It acts primarily on the 3' end of the mRNA, often in conjunction with the decapping machinery, to remove the poly(A) tail and then degrade the mRNA.

The deadenylation-dependent decapping pathway is tightly regulated and involves multiple factors that control its activity. These factors include:

- **RNA-binding proteins:** These proteins can bind to specific sequences in the mRNA and influence the rate of deadenylation and decapping.
- **MicroRNAs (miRNAs):** These small non-coding RNAs can bind to the 3' untranslated region (UTR) of mRNAs and promote deadenylation and decapping.
- **Cellular stress:** Cells can respond to stress by activating pathways that increase the rate of deadenylation and decapping, leading to the degradation of specific mRNAs.

This sophisticated process ensures the controlled degradation of nuclear-transcribed mRNAs, preventing the production of non-functional or potentially harmful proteins, and contributing to the precise regulation of gene expression in eukaryotic cells.'
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Proteins (1)

Compounds (2)