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Post transcriptional modification


Post-transcriptional modification or Co-transcriptional modification is the process in eukaryotic cells where primary transcript RNA is converted into mature RNA. A notable example is the conversion of precursor messenger RNA into mature messenger RNA (mRNA) that occurs prior to protein translation. The process includes three major steps: addition of a 5' cap, addition of a 3' poly-adenylation tail, and splicing. This process is vital for the correct translation of the genomes of eukaryotes because the initial precursor mRNA produced during transcription contains both exons (coding or important sequences involved in translation), and introns (non-coding sequences).

The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' polyadenylation, and RNA splicing, which occur in the cell nucleus before the RNA is translated.

Capping of the pre-mRNA involves the addition of 7-methylguanosine (m7G) to the 5' end. To achieve this, the terminal 5' phosphate requires removal, which is done with the aid of a phosphatase enzyme. The enzyme guanosyl transferase then catalyses the reaction, which produces the diphosphate 5' end. The diphosphate 5' end then attacks the alpha phosphorus atom of a GTP molecule in order to add the guanine residue in a 5'5' triphosphate link. The enzyme (guanine-N7-)-methyltransferase ("cap MTase") transfers a methyl group from S-adenosyl methionine to the guanine ring. This type of cap, with just the (m7G) in position is called a cap 0 structure. The ribose of the adjacent nucleotide may also be methylated to give a cap 1. Methylation of nucleotides downstream of the RNA molecule produce cap 2, cap 3 structures and so on. In these cases the methyl groups are added to the 2' OH groups of the ribose sugar. The cap protects the 5' end of the primary RNA transcript from attack by ribonucleases that have specificity to the 3'5' phosphodiester bonds.


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