Scientists have been making rapid progress in understanding RNA interference or RNAi.
Many organisms use RNAi to control genes, and it can also be used as a tool in the laboratory,
and in future, perhaps, as a therapy.
This animation will introduce you to the principles of RNAi
involving two important types of RNA molecule – small interfering RNAs and micro RNAs.
Eukaryotic cells have many sophisticated ways of controlling gene expression.
In the complex environment of a cell, these mechanisms need to be precisely targeted.
There's a group of mechanisms that use small RNA molecules to direct gene silencing. This is called RNAi.
Inside the nucleus, most genes that encode proteins are transcribed by RNA polymerase II.
The primary RNA transcript is processed by splicing and forms a mature messenger RNA,
sometimes called mRNA.
The messenger RNA is then exported from the nucleus into the cytoplasm.
Here, ribosomes catalyse translation of the messenger RNA to form polypeptide chains that fold into proteins.
But this is also where some small RNA molecules can have their silencing effects.
There are several types of regulatory small RNA.
Small interfering RNAs, known as siRNAs, are derived from longer double-stranded RNAs
that are either produced in the cell itself or are delivered into cells experimentally.
The introduction of siRNAs or double-stranded RNA is widely used to manipulate gene expression.
MicroRNAs are another type of small RNA.
Most microRNAs come from RNAs that are transcribed in the nucleus, which then fold and are processed
before being exported into the cytoplasm as double-stranded precursor microRNAs.
The double-stranded precursors of microRNAs and siRNAS bind to Dicer,
which is an endoribonuclease protein that cuts the RNA into short segments.
Most siRNAs and microRNAs are approximately 21 nucleotides long.
The short double-stranded RNA then binds an argonaut protein.
One strand of the RNA is selected and remains bound to argonaut.
This is called the guide strand.
The combination of the RNA and argonaut, along with other proteins,
is called the RNA-induced silencing complex or RISC.
siRNAs direct RISC to bind to specific messenger RNAs.
The targeting is precise because it's determined by a base pairing
between the siRNA and the target messenger RNA.
siRNAs often have perfect complementarity to their target sites.
Once bound, argonaut catalyses cleavage of the messenger RNA, which will then be degraded.
MicroRNAs also guide RISC to messenger RNAs.
Usually, only part of a microRNA, known as the seed, pairs with a target messenger RNA.
This imprecise matching allows microRNAs to target hundreds of endogenous messenger RNAs.
Targeting via microRNA can lead to messenger RNAs being degraded or translation being inhibited.
Argonauts and their small regulatory RNA code factors are found in plants, animals, fungi, and some bacteria,
and their importance in a multitude of biological processes, and as tools, continues to be revealed.