negative regulation of mRNA 3'-end processing

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of mRNA 3'-end processing. [GOC:mah]

Negative regulation of mRNA 3'-end processing is a crucial step in controlling gene expression. This complex process involves a series of molecular events that ensure accurate and efficient termination of transcription and the addition of a poly(A) tail to the 3' end of nascent mRNAs. This tail is essential for mRNA stability, nuclear export, and translation.

Here's a detailed breakdown of the biological process:

1. **Transcription Termination:** The process begins with the termination of transcription, which is mediated by specific sequence elements within the mRNA. These elements signal to the RNA polymerase to detach from the DNA template, halting the production of the RNA transcript.

2. **Cleavage and Polyadenylation:** Once transcription ends, the pre-mRNA undergoes cleavage and polyadenylation. This process involves the recruitment of a multi-protein complex, called the cleavage and polyadenylation factor (CPF), to the pre-mRNA. This complex contains a number of enzymatic activities, including an endonuclease that cleaves the pre-mRNA at a specific site, known as the polyadenylation signal (PAS).

3. **Poly(A) Tail Addition:** Following cleavage, the 3' end of the pre-mRNA is polyadenylated. This process involves the addition of a string of adenine nucleotides (A) to the newly cleaved end. The enzyme responsible for this addition is poly(A) polymerase (PAP).

4. **Negative Regulation:** Negative regulation of mRNA 3'-end processing involves mechanisms that decrease or inhibit the efficiency of this process. This can occur at different stages:
* **Transcription Termination:** Factors can bind to the DNA template or the RNA polymerase itself to hinder transcription termination.
* **Cleavage and Polyadenylation:** Negative regulatory proteins can bind to the CPF, preventing its assembly or function. Some proteins can also directly bind to the PAS, blocking the cleavage and polyadenylation machinery.
* **Poly(A) Tail Addition:** Proteins can inhibit the activity of PAP or block access to the 3' end of the pre-mRNA.

5. **Consequences of Negative Regulation:** Negative regulation of mRNA 3'-end processing can have significant consequences for gene expression:
* **Reduced mRNA Stability:** Decreased polyadenylation can lead to a shorter poly(A) tail, rendering the mRNA more susceptible to degradation.
* **Impaired Nuclear Export:** The poly(A) tail is required for efficient transport of mRNAs from the nucleus to the cytoplasm, where translation occurs.
* **Decreased Translation:** Reduced polyadenylation can negatively impact the translation efficiency of the mRNA.

**Overall, negative regulation of mRNA 3'-end processing is a critical mechanism that finely tunes gene expression, ensuring that appropriate levels of specific proteins are produced in a cell. This intricate process involves a complex interplay of factors that can be modulated to control cellular function and response to various stimuli.**'"

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