Nuclear mRNA Transport

Nuclear mRNA Transport:

Most of the mRNAs in eukaryotes are synthesized as long precursor RNAs in the nucleus.
Until these are processed to functional RNAs they are not transported out of the nucleus. Only processed ones are transported out.
First the pre-mRNAs are associated with certain proteins called hnRNPs which are involved in hnRNA processing; once processing is complete, mRNAs associate with specific proteins, such as Cap binding complex proteins, poly-A binding PAB-II, exon-joint complexes (EJC) and many others, which cover the whole length of mRNA.

Transportation has to take place through a nuclear pore complex (NPC) found in two-unit nuclear membrane.
The pore complex consists of veritable structural proteins as well as transport proteins.
Transport is an active process and specific, not all RNAs are transported out, only those specified and marked are transported.
None of the cytoplasmic RNAs that are transported into cytoplasm return to the nucleus with certain exceptions such as few snRNAs.
RNA synthesis and many such components have to be imported via Nuclear pore complex (NPC).

Transportation of ribosomes, tRNA, snRNA, scRNAs and other NC RNAs and mRNA is highly regulated.
The presence of SnRNPs at splice junction sites in unspliced mRNAs prevents them from transport.
But mRNAs with specific EJC proteins found at exon-exon splice sites are transported. Mutation in one site does not allow transportation but mutations at both sites allow transportation.
Only capped mRNAs are transported.

All mRNA coated with mRNPs show helically coiled forms.
In Chironema titans, in a larva at 11 th day, many genes are expressed in large scale, which appear as chromosomal puffs and Balbiani rings, but one of the transcripts, for a glue protein for the larva, is expressed in massive amounts.
The protein produced is responsible for the larva to glue to the surface of the substrate at the time of pupal transformation.
This mRNA is transported in large amounts.
The transcripts are long and covered with RNPs and coiled.
As they transport across the pore complex, they unwind.
In every active cell huge precursor mRNAs are found.
The mRNAs which contain polyadenylation site and polyA are added.
They are then transported with their cap structure in fore-front and poly-A tail at 3’end.

Transportation is selective and determined by certain nuclear proteins.
Adenoviral transcripts are preferably transported against host mRNAs, because the 5’ ends of these transcripts are associated with E1B and E4 proteins.
During transportation, mRNAs are bound to ribosomes at their 5’end.
In the case of HIV, a full length transcript is not transported until and unless it is associated with a specific REV protein at its Rev Recognizing Elements (RRE) found at 3’ end.
The primary transcript, if it is 9 KB, with first splicing; its size is reduced to 4kb.
This is not transported.
But the second splicing leads to 2kb mRNA; this 2kb mRNA is transported and translated.
The product is REV protein, which moves back into the nucleus and binds to full length mRNA at (Rev Response Element) RRE element; then only the full length HIV mRNA is transported out.
U2 SnRNA transcribed by RNAP-II is transported but U6Sn RNA transcribed by RNAP-III is not transported for it has no cap structure.
Sn RNAs like U1, U2, U4 and U5 are capped.

They move out of the nucleus, where they are further methylated at cap sites (Tri methylation), associate with certain proteins such as SM (aptamers) and then they return to the nucleus.
Many of the mRNPs transported with mRNA into cytoplasm are displaced with cytoplasmic mRNPs and nuclear mRNPs return to nucleus, a good example is PAB-II.
Presence of poly-A or its absence does not matter for mRNA transport from nucleus to cytoplasm
Many different kinds of Thalassemia are mainly due to their failure to transport their mRNAs out of the nucleus, because of mutations at splicing positions or because of the presence of cryptic splicing sites elsewhere.