Biochemistry/Micro RNA(miRNA)

Micro RNAs are small non-coding regions of RNA (usually of around 21 nucleotides in length) that are involved in the regulation of gene expression by the silencing of genes. This occurs through a process called RNA interference (RNAi). Micro RNA base pairs with mRNA by its 5' to the 3'-untranslated region of mRNA to prevent translation of the mRNA strand, resulting in the prevention of protein synthesis. And also by the modification of the mRNA. The interactions of miRNA with mRNA have not been thoroughly analyzed though there is some insight provided by current research. Complete knowledge of how the mechanisms work is still to be discovered, however, studies provide some information about the mechanisms of how miRNAs affect translation and what other factors may take place during this process.

miRNA modification

In order for miRNA to prevent translation it has to undergo through the addition of some proteins. There are two proteins that have been shown to come together with miRNA. These proteins are GW182 protein and either one of the proteins in the AGO family where AGO is short for Argonaute defined as a catalytic protein. The AGO protein family consists of four proteins name AGO1-AGO4. When miRNA comes together with GW182 and one of the AGO proteins, it forms a complex called miRNA-Induced Silencing Complex (miRISC) this complex will serve as the inhibitor of translation.

miRNA and Inhibition of Translation

After the formation of miRISCs, it can inhibit translation at the initiation phase of translation where it inhibits the formation of the ribosome complex (80s complex for eukaryote and the 70s for prokaryote. For eukaryotes, the 80s complex consist of the 40s and the 60s complexes; in order for the 80s complex to form by the binding of the 60s with the 40s, an initiation factor called eIF4F initiation factor is needed. The eIF4F interacts with PABP or Poly A Binding Protein, this interaction results in the recognition of the poly A tail of the open reading frame by the ribosome subunits. miRISC inhibits the recognition of the cap of the open reading frame by the 40s subunit by either repressing eIF4F or PABP thus the 60s subunit does not join the 40s and as a result the mRNA is not translated. Much study has to be done to fully understand the inhibition of translation at the initiation phase. miRISC also inhibit translation at the post-initiation phase although its mechanism is not yet known. Scientists hypothesize that once the 80s ribosome complex is formed, miRISCs separate the 80s subunit through proteolysis causing a ribosome "drop off" and the mRNA strand remains untranslated.

miRNA-induced Decay of mRNA

Interactions between miRISC and mRNA result in mRNA decay by deadenylation and it is influenced especially by the GW182 protein in the miRISC. GW182 protein interaction with a protein complex CCR4-NOT1 deadenylase complex together they remove an adenyl group from the poly A tail. After deadenylation the 5' terminal cap is removed. The mRNA is then degraded and can no longer go through translation. Much of this mechanism is still unknown and it is predicted that other factors take place in this process but have not yet been discovered. Current research has provided only insights to these processes and their mechanisms.

REFERENCES

Fabian, Marc R. Sonenber, Nahun. Filipowicz, Witold. Regulation of mRNA Translation and Stability by microRNAs. The Annual Review of Biochemsitry. 2010