Transcription and RNA Processing

Transcription copies a gene's information from DNA into RNA. In eukaryotes, RNA polymerase II is guided to a gene's promoter region by transcription factors that assemble at sequences like the TATA box, forming a transcription initiation complex. Once assembled, RNA polymerase unwinds a short stretch of the double helix and begins synthesis.

RNA polymerase reads the template strand 3'→5' and synthesizes the new pre-mRNA strand 5'→3', using ribonucleotides (and uracil instead of thymine) rather than deoxyribonucleotides. The resulting transcript has the same sequence as the non-template (coding) strand, except with U replacing T.

As RNA polymerase moves along the gene, it continuously unwinds the DNA ahead of it and allows the strands to re-anneal behind it, synthesizing RNA the entire time. Transcription continues until the polymerase reaches a terminator sequence, signaling release of the completed pre-mRNA transcript and the polymerase itself.

Before leaving the nucleus, eukaryotic pre-mRNA receives two protective modifications. A modified guanine nucleotide (5' cap) is added to the 5' end; it protects the transcript from degradation and helps the ribosome recognize and bind the mRNA during translation initiation.

At the 3' end, a poly-A tail - a long stretch of adenine nucleotides - is added. It similarly protects the transcript from enzymatic degradation, and it assists in export of the mRNA from the nucleus and helps regulate how long the mRNA persists before being translated.

Eukaryotic genes are typically interrupted by introns (non-coding sequences) between the exons (coding sequences). The spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs), recognizes intron boundaries, removes the introns, and ligates the exons together to form mature mRNA.

By including or excluding different combinations of exons, a single pre-mRNA can be spliced in multiple ways to produce many different mature mRNAs - and therefore many different protein products. This alternative splicing is a major reason the roughly 20,000 protein-coding genes in the human genome can generate several hundred thousand distinct proteins.