5' cap

5' cap (also known as the 5' cap structure or simply cap) is a distinctive feature of RNA molecules, specifically messenger RNA (mRNA) in eukaryotic cells, and certain viral RNA molecules. It is a modified form of guanine nucleotide added to the 5' end of an mRNA molecule during the process of RNA transcription. This modification plays a crucial role in RNA stability, RNA splicing, and the initiation of protein synthesis.

Structure

The 5' cap is a nucleotide structure that consists of a guanine nucleotide connected to the mRNA's first nucleotide via a 5'-5' triphosphate bridge. This guanine is methylated on the 7 position, commonly denoted as m7G. In many cases, additional methylations occur on the sugar-phosphate backbone at the 2' position of the first two nucleotides of the mRNA. The full structure is often represented as m7G(5')ppp(5')NmpNp, where N represents any nucleotide and p represents a phosphate group.

Function

The 5' cap has several important functions in the cell:

• Protection from degradation: The cap structure protects the mRNA molecule from enzymatic degradation by exonucleases.
• Promotion of translation: It is recognized by the eukaryotic initiation factors (eIFs), which are necessary for the initiation of translation. The cap structure facilitates the binding of the mRNA to the ribosome, allowing for the translation process to begin.
• Regulation of nuclear export: The cap structure is involved in the export of mRNA from the nucleus to the cytoplasm.
• Splicing enhancement: It enhances the efficiency of pre-mRNA splicing.

Biosynthesis

The 5' cap is added to the mRNA during the process of transcription in a series of enzymatic reactions: 1. The 5' triphosphate end of the nascent mRNA is first hydrolyzed to a diphosphate by an RNA triphosphatase. 2. A guanylyltransferase then adds a GMP (guanosine monophosphate) in a 5'-5' triphosphate linkage to the diphosphorylated 5' end. 3. This guanine is then methylated by a guanine-7-methyltransferase, resulting in the m7G cap. 4. Additional methylations may occur at the 2' position of the subsequent nucleotides by 2'-O-methyltransferase.

Clinical Significance

Alterations in the cap structure or the capping process can lead to various diseases, including cancer and neurodegenerative diseases. Some viruses have evolved mechanisms to mimic or hijack the host's capping process to ensure the stability and translation of their own RNA, making the capping process a potential target for antiviral therapies.

See Also

• RNA splicing
• RNA polymerase
• Translation
• Eukaryotic initiation factor
• Nucleotide