The Great Escape mRNA export

Transcription is the process through which the mRNA is synthesized form the DNA. The process of DNA transcription is similar to DNA replication but the enzymes involved are different. Transcription of DNA into an mRNA through a DNA template is mainly influenced by an enzyme called RNA polymerase. For the RNA polymerase to influence the transcription process, the enzyme must first recognize where the sequence of the gene begins. This will ensure that the enzyme knows where synthesis of the mRNA should start. The ability of the enzyme to recognize the site of initiation in the DNA is due to the presence of the promoter sequence, a sub-unit in the DNA. The promoter sequence which is located at one end of the DNA strands instructs the enzyme where and in what direction to start synthesizing the mRNA. This is followed by unwinding of the double helix strand by the enzyme and the mRNA strand is synthesized, complimentary to the DNA strands. This process is unidirectional. Although the transcription process is similar to the DNA replication which has been well studied, it is not clear what events or processes are responsible for instructing the enzyme to stop transcription process (Peters, pg 235).    

After DNA transcription is complete, the resultant RNA is not ready for export to the ribosome and the subsequent translation process. The mRNA produced undergoes a series of modification before it is exported to outside the nucleus. The modifications are called post transcription modification. However, this processes are absent in some non eukaryotic organisms whose mRNA is ready for export after transcription and may not require any modification. In the eukaryotic organisms, research indicates that a series of modification process takes place before the mRNA is exported to the ribosome. The export of the mRNA from the nucleus to the cytoplasm across the membrane takes place through the nuclear pore complex. It is essential for the transcript to be modified in a way that it will be recognized by the nuclear pore complex. (Grlich and Mattaj, pg 1515).

Post transcriptional modifications are series of processes through which the precursor mRNA is converted into a mature mRNA. These processes are essential for the correct translation of the genetic material in protein synthesis in eukaryotic cells. In these cells, the primary mRNA or the precursor mRNA contains the exons and the introns. The exons describe the coding segments of the mRNA precursor while the introns consist of the non coding segments. Before the mRNA molecule is exported for export, there are three main modifications that take place. These includes 5 capping, 3 polyadenylation and finally splicing.

The capping of the precursor mRNA is a process through which a 7- methylguanosine is added to the 5 end of the precursor. This is done by first removing the phosphate on the 5 end using the phosphatase enzyme followed by formation of disphosphate on the 5 terminal which is catalyzed by guanosyl transferase. The GTP molecule is then added to the diphosphate terminal leading to lose of the disphospate. This process is also catalyzed by the enzyme guanosyl transferase (Moore, M.S and Blobel, pg 662). The process leads to 5 to 5 linkage of between the triphosphate groups in the guanine residue. The nitrogen in the 7 position is then methylated using SAM (S-adenosyl methionine). Incase no other capping modification happens apart from the methyl group added on nitrogen at seventh terminal, the mRNA precursor is known as cap 0. Otherwise more capping can be done where SAM can be used to add methyl group on the ribose sugar groups of the neighboring nucleotides to form a cap 1 mRNA precursor. Subsequent methylation of the ribose groups of the nucleotides along the mRNA molecule leads to formation of cap 2, cap 3 cap 4 and so on. It should however be noted that these subsequent additions of methyl groups downstream are added at the hydroxyl groups at position 2 of the ribose sugar molecule. This capping at the fifth position introduces a protecting group in the mRNA to reduce the likelihood of attack by the 3 5 phosphodiesters in the ribonucleaseses which are found in the eukaryotic cells (Izaurralde, pp 710).    

Studies suggests that there exists a  capping enzyme complex, consisting of the enzyme units involved in the capping process, which is incorporated on the RNA polymerase and ensures that capping continues as the transcription goes on. The enzyme complex through a series of processes caps the first terminal as soon as it emerges. This capping enzyme complex can bind to an RNA polymerase only, the enzyme responsible for the transcription process, to ensure that only the transcripts are capped in the nucleus. Other than protecting the 5 terminal of the mRNA in the translation process, the capping regulates the export of the RNA by ensuring that only the capped mRNA is exported. The cap binding complex, which regulate the export of mRNA from the nucleus can only bind to mRNAs which are capped at the fifth terminal. This is very important because the nuclear pore can only recognize the cap binding complex. The nuclear pore then exports the mRNA to the cytoplasm and the position of the cap binding complex is taken by the translation factors (Peters, pg 236).

Another post transcription modification of the mRNA precursor is the addition of a 200 units of adenosine monosphospates tail. The process starts with cleavage at the 3 terminal of the strand which is followed by a process of adenylation. This process is triggered by the presence of a polyadenylation signal sequence near the 3 terminal of the precursor followed by a second signal. The first signal is designated by 5AAUAAA3 while the second signal is designated by 5CA3 on the precursor RNA strand. The cleavage always takes place at the second signal sequence. A strand rich in GU sequence downstream is also essential in the polyadenylation process. This process begins as the transcription process ends. Because the cleavage happened specifically at the 3 most position on the poly (A) chain, the transcripts formed are homogeneous. However, some cells have been found to exhibit alternate cleavage where adenylation takes place at other sites within the site producing a variety of transcripts from a single precursor (Segref, pg 3256).

Splicing is also a major process that takes place before triplicates are exported to the cytoplasm. It involves removing the introns, the non coding segments, on the precursor. This process leaves the exons which are reconnected into a single molecule with continuous proteins codes. This splicing process can occur at any point during the transcription process depending on the protein being synthesized. The process is catalyzed by an enzyme complex known as splicesome. Following this modifications, the pre mRNA molecule forms complexes with the export proteins to form RNP. The formation of these complexes is essential for the recognition of the mRNA by the nuclear pore complexes. The adapter proteins and the export receptor TAP are the most important components of the RNP complex. The Export receptor TAP component causes the export of the mRNA to the cytoplasm by interacting with the adaptor protein and the nuclear pore complex. The adaptor protein on the other hand binds directly to the mRNA being exported (Huang and Joan, pp 900).  


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