Post-transcriptional modification

Post transcriptional modification is a genetic process in cell biology by which, in eukaryotic cells, primary transcript RNA is converted into mature RNA. It is most often associated with the conversion of precursor messenger RNA into mature messenger RNA (mRNA), which is also known as splicing, during the larger process of protein synthesis. This process is vital for the efficient and correct translation of the genome. It should not be confused with posttranslational modification, which occurs after translation in order to modify proteins further.

The three main modifications are 5' capping, 3' polyadenylation, and RNA splicing. While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as heterogeneous ribonucleoprotein particles (hnRNPs).

Addition of the 5' cap is the first step in pre-mRNA processing. This step occurs co-transcriptionally, that is, while the RNA molecule is still being transcribed, after the growing RNA strand has reached 30 nucleotides. The process is catalyzed by a capping enzyme that associates with the carboxyl-terminal domain of RNA polymerase II, the main enzyme involved in mRNA transcription.

The second step is the cleavage of the 3' end of the primary transcript following by addition of a polyadenosine (poly-A) tail. This end of the pre-mRNA contains a sequence of around 50 nucleotides that acts as a signaling region recognised by a protein complex. The protein complex promotes association of other proteins including those involved in the cleavage and Polyadenylate Polymerase (PAP), the enzyme responsible for the addition of the tail. PAP binding is required before the cleavage can occur, enforcing the tight coupling of the two events.

RNA splicing is the process by which introns, regions of RNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule. Although most RNA splicing occurs after the complete synthesis and end-capping of the pre-mRNA, transcripts with many exons can be spliced co-transcriptionally. The splicing reaction is catalyzed by a large protein complex called the spliceosome assembled from proteins and small nuclear RNA molecules that recognize splice sites in the pre-mRNA sequence. Many pre-mRNAs, including those encoding antibodies, can be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. This process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount of DNA.