Question

Why do eukaryotic mRNAs have to be "processed" whereas most prokaryotic RNAs do not? (Section 4.9)

Short answer

Eukaryotic mRNAs require processing for stability and maturity due to the compartmentalization between the nucleus and cytoplasm, while prokaryotic RNAs do not.

Step-by-step solution

Understand RNA Processing

In eukaryotic cells, the primary RNA transcript undergoes several modifications before it becomes a mature mRNA that can be translated into a protein. These modifications include capping, polyadenylation, and splicing.

Define Capping

Capping involves the addition of a 5' cap to the beginning of the RNA transcript. This cap protects the RNA from degradation and helps in the initiation of translation.

Define Polyadenylation

Polyadenylation is the addition of a poly-A tail to the 3' end of the RNA transcript. This tail also protects the RNA from degradation and plays a role in the export of the mRNA from the nucleus.

Define Splicing

Splicing removes the non-coding regions called introns from the RNA transcript. The remaining coding regions, called exons, are joined together to form the final mRNA structure.

Contrast with Prokaryotic RNA

In prokaryotic cells, RNA transcripts do not require such extensive processing. Prokaryotic mRNAs are usually ready for translation immediately after transcription without needing capping, polyadenylation, or splicing.

Reason for Eukaryotic RNA Processing

Eukaryotic cells have compartmentalization, meaning the nucleus and cytoplasm are separated. Processing the RNA ensures it is stable and mature when exported from the nucleus to the cytoplasm for translation.

Key concepts

Capping

Capping is the first modification that occurs to the primary RNA transcript in eukaryotes. This process involves adding a special nucleotide, called a 5' cap, to the beginning (5' end) of the RNA.
The 5' cap is a modified guanine nucleotide which is added soon after the RNA transcript begins to be synthesized.
This cap serves multiple crucial functions:

• Protection: It shields the RNA from enzymatic degradation.
• Translation Initiation: It aids in the binding of the mRNA to the ribosome, facilitating the onset of translation.
• Processing: It helps in further processing events like splicing and polyadenylation.

Without capping, the mRNA would be rapidly degraded, and protein synthesis would be inefficient.

Polyadenylation

Polyadenylation is another key modification that happens to the RNA transcript. This is the addition of a long chain of adenine nucleotides, known as the poly-A tail, to the 3' end of the RNA.
The poly-A tail is added after the RNA is cleaved at a specific site downstream of the coding sequence.
Functions of the poly-A tail include:

• Stability: It prevents degradation by exonucleases, extending the life of the mRNA.
• Export: It aids in the transport of the mRNA out of the nucleus and into the cytoplasm.
• Translation: It enhances the efficiency of translation by interacting with proteins that bind to the ribosome.

The presence of a poly-A tail is critical for the mRNA's stability and functionality.

Splicing

Splicing is a significant step in the processing of the primary RNA transcript. Eukaryotic genes often contain non-coding sequences called introns, which need to be removed.
The remaining coding sequences, known as exons, are joined together.
Key aspects of splicing include:

• Spliceosomes: These are complex molecular machines that facilitate the removal of introns and ligation of exons.
• Alternative Splicing: Different combinations of exons can be joined together, allowing a single gene to encode multiple proteins.

Splicing ensures that the mRNA encodes a continuous sequence of amino acids for accurate protein synthesis.

mRNA Stability

mRNA stability plays an essential role in determining how long an mRNA molecule remains functional in the cell. The stability of an mRNA affects the level of protein that can be synthesized from it.
Factors influencing mRNA stability include:

• 5' Cap: Protects the mRNA from degradation by exonucleases.
• Poly-A Tail: Length of the tail can influence the lifespan of the mRNA.
• RNA-Binding Proteins: Proteins can bind to the mRNA and protect it from degradation or target it for destruction.

Ensuring mRNA stability is crucial for proper gene expression and efficient translation.

RNA Export

RNA export is the process by which the mature mRNA is transported from the nucleus to the cytoplasm, where protein synthesis occurs.
This process occurs through the nuclear pore complexes (NPCs) and involves several steps:

• Recognition: Export receptors recognize and bind to mature mRNA.
• Transport: The mRNA-receptor complex is guided through the NPC.
• Release: Once in the cytoplasm, the mRNA is released for translation.

Efficient RNA export is essential for the cell as it ensures that the mRNA reaches the ribosomes in the cytoplasm where proteins are synthesized.
Anomalies in RNA export can lead to diseases and cellular dysfunction.