MicroRNAs
Contents
Introduction
MicroRNAs take part in the gene silencing by being a component of the multi-protein RISC, the RNA-induced silencing complex which silences genes.
A nature conclusion of this statement is that microRNAs are particularly involved in down-regulation of genes. Nevertheless, they are also associated with up-regulation as well.
MicroRNAs make the journey (i.e. their biogenesis) in the nucleus of the cell and move out and submit to various changes. We start with pri-microRNA, then pre-microRNA which gets split (by DICER usually) the RNA and folds it back on itself rendering it as double stranded RNA (don't forget RNA is usually single stranded) this fold is achieved thourhg a hairlop arrangement. The loop is then cut off and one of the strands either the plain "-5p" or the reverse strand "-3p" is chosen (it's poorly understood how this choosing takes place) is loaded onto the ARGONAUT protein, whereupon it begins its operational life as is now called mature microRNA.
Tools
As the above description suggests, how and where a pre-microRNA olds back on itself is a critical point, and a well known which uses free energy calculations is RNAfold from the Vienna RNA package.
Relevant Papers
"Predicting effective microRNA target sites in mammalian mRNAs"
By Agarwal et al eLife 2015 , link here
- miRNA targets involve pairing the miRNA seed region with complementary site on the mRNA in question.
- A canonical site on an mRNA is the exact complement of the miRNA seed. Most but not all bindings are canonical.
- miRNAs often bind to mRNA and degrade it (i.e. represses it) so that it produces less protein.