Northern blot

Suppose you want to know not just whether a gene exists in the genome, but whether a cell is actually using it right now — and how much. The currency of gene activity is messenger RNA: an active gene makes lots of its mRNA, a silent gene makes little or none. A Northern blot measures exactly that — the amount and size of a specific RNA in a sample.

It is the Southern blot's method applied to RNA instead of DNA. You extract RNA from cells, separate it by size on a gel, blot it onto a membrane, and probe it with a labelled single-stranded nucleic acid complementary to the RNA you care about. The probe hybridizes only to the matching transcript, lighting up a band. The position of the band tells you the transcript's size (useful for spotting alternative splicing, where one gene yields RNAs of different lengths), and the brightness of the band tells you roughly how much of that RNA the cell contains — a direct readout of how strongly the gene is being expressed.

Northern blots were for years the standard way to study gene expression: compare a healthy tissue with a diseased one, or cells before and after a treatment, and see which genes turn up or down. They also reveal transcript size and splice variants in a single picture. Today RNA-seq and quantitative PCR are faster and more sensitive and have largely replaced the Northern blot, but the technique remains a clear, visual illustration of the idea that gene expression can be measured by quantifying RNA. (The name is a pun on Southern, not a compass point.)