RNA Processing in Eukaryotes

Biology: IB Diploma Higher Level, topic 1.3.4

Before the information in eukaryotic mRNA is translated into protein, it is modified or edited in several ways

The initial mRNA molecule produced in eukaryotic transcription is known as "pre-mRNA".
The eukaryotic pre-mRNA undergoes extensive processing before it is ready to be translated.
The additional steps involved in eukaryotic mRNA maturation create a molecule with a much longer half-life than a prokaryotic mRNA.
Eukaryotic mRNAs last for several hours, whereas the typical E. coli mRNA lasts no more than five seconds.

While the pre-mRNA is still being synthesized, a 7-methylguanosine cap is added to the 5' end of the growing transcript by a phosphate linkage.
This is sometimes more simply called a "GTP cap".
This moiety (functional group) protects the nascent mRNA from degradation.
In addition, factors involved in protein synthesis recognize the cap to help initiate translation by ribosomes.

Once elongation is complete, the pre-mRNA is cleaved by an endonuclease between an AAUAAA consensus sequence and a GU-rich sequence.
This leaves the AAUAAA sequence on the pre-mRNA.
An enzyme called poly-A polymerase then adds a string of approximately 200 A residues, called the poly-A tail.
This modification further protects the pre-mRNA from degradation.
The poly-A tail also signals the export of the cellular factors that the transcript needs to the cytoplasm.

Eukaryotic genes are composed of exons and introns.
Exons correspond to protein-coding sequences.
Introns do not encode functional proteins. They may be involved in gene regulation but are removed from the pre-mRNA during processing.
The process of removing introns and reconnecting exons is called splicing.

Splicing removes and degraded introns while the pre-mRNA is still in the nucleus.
Splicing occurs by a sequence-specific mechanism that ensures introns will be removed and exons rejoined.
The splicing of pre-mRNAs is conducted by complexes of proteins and RNA molecules called spliceosomes.
Spliceosomes are composed of proteins and RNA molecules called snRNAs.
Spliceosomes recognize sequences at the 5' and 3' end of the intron.

Splicing can produce many different mRNA molecules from a single pre-mRNA molecule.
This is because the pattern of exons and introns can be reordered during splicing.
This is known as alternative splicing.
Alternative splicing plays a role in gene regulation and increases the diversity of proteins that can be produced from a single gene.

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