11.4: Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific roles during different stages of the mRNA transport. For example, mRNA is exported through the nuclear pore complexes with the help of an exporter protein, which is a heterodimer of nuclear export factor 1 and nuclear export transporter 1. These proteins recognize specific nucleotide sequences or stem-loop structures formed by the mRNA and can bind different types of mRNA with similar binding features.
mRNA is usually only transported from the nucleus after it is fully processed. However, some RNA from specific viruses, such as the Human Immunodeficiency Virus (HIV), can circumvent this rule. HIV transfers some of its intron carrying pre-mRNA from the nucleus to the cytoplasm with the help of a protein called Rev. Rev is encoded by HIV RNA and binds to the specific sequences present within the pre-mRNA introns as well as the nuclear export receptor. This facilitates the transport of the intron-carrying pre-mRNA to the cytoplasm.
Cytoplasmic Fate of the transported mRNA
Once transferred in the cytoplasm, the further journey of the mRNA within the cytoplasm largely depends on whether it encodes organelle-specific, secretory, or cell surface protein. In the case of organelle-specific proteins, the protein produced will be transported to the respective organelle with the help of a signal peptide sequence. On the other hand, if a particular mRNA produces a secretory protein, the mRNA will be directed to the endoplasmic reticulum along with the associated ribosome and nascent peptide. This will happen during the initial stages of the protein synthesis, and the transferred mRNA- ribosome complex will remain on the endoplasmic reticulum until the protein synthesis is complete.
In contrast, some mRNAs are transported to specific locations in the cytoplasm before starting protein production. Such localization signals, known as zip-code regions, are present in the 3' untranslated regions of the mRNA. mRNA transport to the target location can be either random or directed by cytoskeletal filaments. Such mRNA localization not only helps cells to produce high concentrations of proteins near to the target location, but it also eliminates the need for the cell to use resources to transport the protein to its final destination.