7-methylguanosine cap

As mentioned above, mammahan mRNA molecules contain a 7-methylguanosine cap structure at their 5 terminal, and most have a poly(A) tail at the 3 terminal. The cap stmcmre is added to the 5 end of the newly transcribed mRNA precursor in the nucleus prior to transport of the mELNA molecule to the cytoplasm. The S cap of the RNA transcript is required both for efficient translation initiation and protection of the S end of mRNA from attack by S —> S exonucleases. The secondary methylations of mRNA molecules, those on the 2 -hydroxy and the N of adenylyl residues, occur after the mRNA molecule has appeared in the cytoplasm. 

A 7-methylguanosine cap is added to the 5 end while the RNA molecule is still being synthesized. The cap structure serves as a ribosome-binding site and also helps to protect the mRNA chain from degradation. 

Posttranscriptional modification of mRNA showing the 7-methylguanosine cap and poly-A tail. 

Capping of eukaryotic mRNA. (a) Enzymatic reactions required for 50 capping SAM is -S -adenosyl methionine and SAC is -S -adenosyl homocysteine, (b) Structure of 7-methylguanosine cap. 

Poliovirus RNA in many respects looks like a typical eukaryotic mRNA with a polyadenylated 30 tail and a protected 50 terminus. However, the poly (A) tail is not added by the action of poly (A) polymerase, but instead is encoded in the viral genome. In addition, the 50 end does not contain a 7-methylguanosine cap, but rather a covalently attached viral protein called VPg that has a phosphodiester linkage between a tyrosine residue in VPg and a uridine in the viral RNA. 

Postranscriptional modification of RNA is important in RNA function. One of the more important postranscriptional modifications is the synthesis of a 7-methylguanosine cap on the 5 end of eukaryotic mRNAs which are important in the efficient translation of these messengers (10, 32). Because GTP is involved in the biosynthesis of the cap, it may be involved in regulating the rate of synthesis. 

Figure 35-10. The cap structure attached to the 5 terminal of most eukaryotic messenger RNA molecules. A 7-methylguanosine triphosphate (black) is attached at the 5 terminal of the mRNA (shown in blue), which usually contains a 2 -0-methylpurine nucleotide.

The primary transcripts generated by RNA polymerase II—one of three distinct nuclear DNA-depen-dent RNA polymerases in eukaryotes—are promptly capped by 7-methylguanosine triphosphate caps (Figure 35-10) that persist and eventually appear on the 5 end of mature cytoplasmic mRNA. These caps are necessary for the subsequent processing of the primary transcript to mRNA, for the translation of the mRNA, and for protection of the mRNA against exonucleolytic attack. 

Sequence analysis of the 5 -ends of viral and nuclear mRNA molecules reveals that these are frequently capped , with an unusual structure in which 7-methylguanosine is joined by a (5 - 5 ) triphosphate link to a 2 -0-methyl nucleoside moiety which is the first residue in the (3 ->5 )-linked polynucleotide chain.166-168 The presence of this cap structure is required for ribosomal binding and translation to take place,167- 168 and 7-methylguanosine-5 -phosphate inhibits translation by preventing formation of the ribosome-mRNA complex.169... 

Both ends of mRNA molecules are chemically modified. The 5 end is capped by 7-methylguanosine triphosphate. This modified guanine cap helps to protect the mRNA from attack by hydrolytic enzymes. Beyond that, the 7-methylguanosine triphosphate cap acts as a recognition element for ribosomes. The 3 end is modified by the addition of a poly A tail. This may consist of as few as 30 or as many as 200 adenine nucleotides. 

FIGURE 26-12 The 5 cap of mRNA. (a) 7-Methylguanosine is joined to the 5 end of almost all eukaryotic mRNAs in an unusual 5, 5 -triphosphate linkage. Methyl groups (pink) are often found at the 2 position of the first and second nucleotides. RNAs in yeast cells lack the 2 -methyl groups. The 2 -methyl group on the second nucleotide... 

Most eukaryotic mRNAs have a 5 cap, a residue of 7-methylguanosine linked to the 5 -terminal residue of the mRNA through an unusual 5, 5 -triphosphate linkage (Fig. 26-12). The 5 cap helps protect mRNA from ribonucleases. The cap also binds to a specific capbinding complex of proteins and participates in binding of the mRNA to the ribosome to initiate translation (Chapter 27). 

Expression of genetic information by transcription. [Note RNAs shown are eukaryotic.] me-7Gppp = 7-methylguanosine triphosphate cap, described on p. 414. AAA = poly-A tail, described on p. 414. 

The first processing event (Eq. 28-6) for most of the pre-mRNA and snRNA transcripts made by RNA polymerase II is addition to the 5 end of a "cap," a terminal structure containing 7-methylguanosine from which a proton has dissociated to form a dipolar ion.563 565 The cap structure may be abbreviated 5 -m7G(5 )pppNm —. The 5 terminal ribose is often methylated on 02 , as shown below. More complex caps are methylated at additional sites, e.g., the guanine may be dimethylated on the 2-NH2 group.551 Most snRNAs, including the U1-U5 and U7-U13 snRNAs, have such 2,2,7-trimethylguanosine... 

Structure of the 5 methylated cap of eukaryotic mRNA. A 7-methylguanosine (in red) is attached through a triphosphate linkage formed between its 5 -OH and the 5 -OH of the terminal residue in... 

We first describe the synthesis of unsymmetrical a.y-dinucleoside triphosphates involving 7-methylguanosine. For the construction of the terminal cap structure, there might be two possible reaction modes where an activatable protecting group (X) was introduced into a nucleotide by direct displacement with phosphate hydroxyl group (Method A) and by pyrophosphorylation between Xp and pN (Method B). 

Immediately after transcription, the 5 phosphate is removed, guanosyl transferase adds a G residue linked via a 5 -5 covalent bond, and this is methylated to form a 7-methylguanosine (m7G) cap (methylated in N-7 position of the base). The ribose residues of either the adjacent one or two nucleotides may also be methylated by methyl group addition to the 2 OH of the sugar. The cap protects the 5 end of the mRNA against ribonuclease degradation and also functions in the initiation of protein synthesis. 

A cap is a 7-methylguanosine residue that is posttranslationally added to the 59 end of a eukaryotic. ... 

Schematic drawing showing production of eukaryotic mRNA. The primary transcript is capped before it is released. Then its 3 -OH end is modified, and finally the intervening regions are excised. MeG, 7-methylguanosine. Two nucleotides whose riboses may be methylated.

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