Question

How do sequences in the mRNA affect the molecule’s stability? What is an example of a stabilizing element, and an example of a destabilizing element?

Answer 1

The sequence and structure of the mRNA affect the stability of mRNA. The ends are protected from degradation with post transcription modification that includes 5' capping and 3' tailing from nucleases. The destabilization element refers to its introduction in the mRNA sequence may cause the degradation of the mRNA and it is not necessary that its removal turns back to its stability.

• The 5' capping involves the addition of 5-Methyl Guanosine and 3' tailing involve the addition of Poly (A) tail at the end. These modifications help the mRNA to protect from degradation.
• The destabilizing element present at the 3' end that is an untranslated region followed by the translation termination codon. These types of sequences reduce the half-life of the mRNA and reduce the expression also.
• The nonsense mutation causes the mutation in the mRNA that creates a stop codon that triggers the degradation of the mRNA.
• In yeast, the deadenylation encourages the destabilization of the mRNA. It causes the loss of poly(A)-binding protein.
• In some of the unstable mRNAs, there is the presence of an AU-rich sequence/element ( ARE) of ~50 bases located at 3' trailer end. he pentanucleotide AUUUA which is the consensus sequence in the ARE repeated several times. The ARE is responsible for the destabilization which can take place by a two-stage process:

1. The deadenylation of mRNA
2. Degradation

• The stabilization can also be achieved by inhibiting the destabilizing element. The transferrin has an Iron response element (IRE) that regulate the mRNA concentration in the presence of iron. It is located in the 3' non translated region that forms a stem-loop structure. This stem-loop structure bind to the protein to regulate the mRNA expression which is controlled by the iron. When the protein bind to the binds to the IRE sequence then there is inhibition of the nearby destabilizing elements.

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