Five-prime cap

Five-prime cap (5′ cap) is a distinctive structural feature of RNA molecules, specifically of messenger RNA (mRNA) in eukaryotes and in various other organisms that play a crucial role in gene expression. The 5′ cap consists of a guanine nucleotide connected to mRNA via an unusual 5′ to 5′ triphosphate linkage. This guanine is methylated on the 7 position directly after transcription in the nucleus. The presence of the cap protects the nascent mRNA from degradation and assists in ribosome binding during translation.

Structure and Formation

The 5′ cap is added to the mRNA during the process of transcription and is one of the first modifications of the pre-mRNA in eukaryotic cells. The formation of the cap is catalyzed by a series of enzymes. Initially, an enzyme known as RNA triphosphatase removes the gamma phosphate from the 5′ end of the pre-mRNA. Subsequently, guanylyltransferase adds a GMP (guanosine monophosphate) in a 5′ to 5′ triphosphate linkage. This guanosine is then methylated by guanine-7-methyltransferase, resulting in the formation of the 5′ cap structure. In some cases, additional methylations may occur on the ribose sugar of the first few nucleotides of the mRNA, further stabilizing the mRNA molecule.

Function

The 5′ cap has several key functions in mRNA metabolism and gene expression:

• Protection from degradation: The cap structure protects the mRNA from exonucleases, enzymes that could degrade the mRNA from its ends.
• Promotion of translation: The cap is recognized by specific proteins that are involved in the initiation of translation. These cap-binding proteins, such as eIF4E (eukaryotic initiation factor 4E), facilitate the binding of the ribosome to the mRNA, thereby promoting protein synthesis.
• Regulation of nuclear export: The cap structure also plays a role in the export of mRNA from the nucleus to the cytoplasm, a critical step in gene expression.
• Splicing: In eukaryotes, the 5′ cap is involved in the removal of introns from pre-mRNA through the process of splicing.

Clinical Significance

Alterations in the mechanisms of capping and the recognition of the cap structure can lead to various diseases, including cancer. For instance, changes in the activity of cap-binding proteins have been associated with the dysregulation of gene expression in tumors. Additionally, some viruses have evolved mechanisms to mimic or hijack the host's capping machinery to ensure the efficient translation of viral proteins.

See Also

• RNA splicing
• Gene expression
• Messenger RNA
• Translation (biology)
• Transcription (genetics)