What is RNAi?

Biotechnology & Healthcare Molecular Biology
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What is RNAi?

RNA stands for ribonucleic acid, a nucleic acid present in all living cells. RNAi  is short for “RNA interference” and it refers to a phenomenon where small pieces of RNA can shut down protein translation by binding to the messenger RNAs that code for those proteins.

RNA interference is a natural process with a role in the regulation of protein synthesis and in immunity. It’s also a potent tool for the exploration and manipulation of gene expression.

The small pieces of RNA that enable RNA interference come in two varieties:

  • Small interfering RNA (siRNA)
  • MicroRNA (miRNA).

Both varieties are pieces of RNA – approximately 22 nucleotides long – but they differ in their role, specificity and how they are synthesized.

siRNAs

siRNAs are highly specific and usually synthesized to reduce the translation of specific messenger RNAs (mRNAs). This is done to reduce the synthesis of particular proteins. They form from double-stranded RNA transcribed and then cut to size in the nucleus before releasing into the cytoplasm.

miRNAs

miRNAs are a more general suppressive tool, formed from single-stranded RNA precursors and characterized by their distinctive hairpin shape.

How RNAi Works

Regardless of whether siRNAs or miRNAs are involved, RNA interference works in approximately the same way.

These small RNA molecules connect to and activate protein complexes, most notably the RNA-induced silencing complex (RISC). Once bound, they can bind to their target mRNAs and both physically prevent ribosomes from continuing to synthesize the associated protein and mark that mRNA for destruction.

This process serves important roles in regulating protein synthesis, whether in general or of specific proteins, by acting as a layer of control separate and downstream from the various genes that regulate transcription itself. In particular, RNA interference prevents mRNAs from outlasting their need, by disposing of them before they might otherwise naturally degrade.

RNA interference also serves a role in protecting cells from viruses, by attacking their mRNAs and sometimes even their RNA-based genomes before the cell’s synthesis machinery can manufacture viral proteins.

RNAi’s Role in Fighting Disease

RNA interference shows fascinating promise as a tool in molecular biology. The relationship between the target mRNA sequence and the sequence required for a functional siRNA or miRNA is well-established, allowing scientists to synthesize interfering RNAs as needed.

These RNAs then inhibit protein synthesis in a less complicated and invasive way than altering the genetic code. When a protein’s function is still mysterious, such interference helps scientists observe what happens in its absence, and from there, learn what it does.

Furthermore, RNA interference enables “knockdown” experiments, in which synthesis of a protein is reduced but not eliminated, as it would be if its gene were simply cut out or turned off.

As a new area of protein synthesis regulation to explore, RNA interference is a fertile area of inquiry in many sub-fields of medicine. It may become an important weapon against increasingly antibiotic-resistant bacterial infections, inhibiting bacteria in an entirely different way than antibiotics do.

It is another possibility to explore in the fight against cancer, disabling protein synthesis inside cancer cells until they die or at least cease reproducing.

It can potentially target malfunctioning or over-expressed proteins in a variety of body cells, addressing a wide variety of health conditions that are otherwise difficult to treat.

By targeting mRNAs rather than proteins, RNA interference stands to work around the cross-reactivity and resistance that can complicate treatment for many conditions. This can make medicine for even complex situations more and more specific while reducing side effects.

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