RNA capping

In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped. In molecular biology, the five-prime cap (5′ cap) is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is highly regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped. In eukaryotes, the 5′ cap (cap-0), found on the 5′ end of an mRNA molecule, consists of a guanine nucleotide connected to mRNA via an unusual 5′ to 5′ triphosphate linkage. This guanosine is methylated on the 7 position directly after capping in vivo by a methyltransferase. It is referred to as a 7-methylguanylate cap, abbreviated m7G. In multicellular eukaryotes and some viruses, further modifications exist, including the methylation of the 2′ hydroxy-groups of the first 2 ribose sugars of the 5′ end of the mRNA. cap-1 has a methylated 2'-hydroxy group on the first ribose sugar, while cap-2 has methylated 2'-hydroxy groups on the first two ribose sugars, shown on the right. The 5′ cap is chemically similar to the 3′ end of an RNA molecule (the 5′ carbon of the cap ribose is bonded, and the 3′ unbonded). This provides significant resistance to 5′ exonucleases. Small nuclear RNAs contain unique 5'-caps. Sm-class snRNAs are found with 5'-trimethylguanosine caps, while Lsm-class snRNAs are found with 5'-monomethylphosphate caps. In bacteria, and potentially also in higher organisms, some RNAs are capped with NAD+, NADH, or 3'-dephospho-coenzyme A. In all organisms, mRNA molecules can be decapped in a process known as messenger RNA decapping. The starting point for capping with 7-methylguanylate is the unaltered 5′ end of an RNA molecule, which terminates at a triphosphate group. This features a final nucleotide followed by three phosphate groups attached to the 5′ carbon. The capping process is initiated before the completion of transcription, as the nascent pre-mRNA is being synthesized. The mechanism of capping with NAD+, NADH, or 3'-dephospho-coenzyme A is different. Capping with NAD+, NADH, or 3'-dephospho-conenzyme A is accomplished through an 'ab initio capping mechanism,' in which NAD+, NADH, or 3'-desphospho-coenzyme A serves as a 'non-canonical initiating nucleotide' (NCIN) for transcription initiation by RNA polymerase and thereby directly is incorporated into the RNA product. Both bacterial RNA polymerase and eukaryotic RNA polymerase II are able to carry out this 'ab initio capping mechanism.' For capping with 7-methylguanylate, the capping enzyme complex (CEC) binds to RNA polymerase II before transcription starts. As soon as the 5′ end of the new transcript emerges from RNA polymerase II, the CEC carries out the capping process (this kind of mechanism ensures capping, as with polyadenylation). The enzymes for capping can only bind to RNA polymerase II, ensuring specificity to only these transcripts, which are almost entirely mRNA.