3.6 Non-coding DNA and Product Processing

Only a small fraction of a eukaryotic genome encodes polypeptide sequence. Non-coding DNA includes promoters, enhancers, genes for functional RNAs, introns, repeated sequences, centromeric regions and telomeres. Some has known regulatory or structural roles; some may have no current function. The older label “junk DNA” is misleading when it implies that every non-coding base is useless, but it is equally unsafe to claim that every base has a demonstrated function.

Tandem repeats contain a short sequence repeated head-to-tail. Repeat number can vary among individuals, which makes selected VNTR and STR loci useful for profiling. Some repeated or otherwise non-coding sequences are conserved across species, suggesting that natural selection has preserved a function such as gene regulation or chromosome organization. Conservation is evidence of constraint, though experiments are still needed to identify the precise role.

Telomeres are repeated DNA sequences associated with proteins at chromosome ends. They protect chromosome ends from degradation and from being treated as broken DNA. Conventional replication cannot fully copy the end of a linear lagging strand, so telomeres tend to shorten in many somatic cell lineages. Telomerase can extend them in germ cells, many stem cells and many cancer cells. Telomere shortening is linked to replicative limits but is not a simple universal clock for organismal ageing.

A eukaryotic primary transcript often includes exons and introns. A spliceosome removes introns and joins exons to produce mature mRNA. The terms are best understood operationally: introns are removed from the RNA, while the retained exons are represented in the mature transcript. Introns are transcribed but not translated; promoter and enhancer DNA usually are not part of the transcript at all.

Alternative splicing joins different combinations of exons from one primary transcript. The resulting mature mRNAs can encode related polypeptides with different domains and functions. This helps explain how a eukaryotic proteome can contain far more protein forms than the number of protein-coding genes. Alternative splicing does not change the gene's DNA sequence and does not mean that exons can be assembled in arbitrary orders.

A modified guanine cap is added to the 5′ end and a poly-A tail to the 3′ end of many eukaryotic mRNAs. These structures support nuclear export, protect the transcript from rapid degradation and assist recognition by translation machinery. Their presence does not make an mRNA permanent: regulated decay is a major way to change how long a transcript can support protein synthesis.

Translation determines primary amino-acid sequence, after which interactions among backbone and side chains drive folding into secondary and tertiary structures. Some proteins assemble from several polypeptide subunits. Chaperone proteins can assist correct folding. Location and chemical environment matter: a membrane protein, secreted enzyme and nuclear regulator require different targeting and processing pathways.

Post-translational changes alter activity, stability, interactions or destination. Phosphorylation can switch an enzyme or signalling protein between functional states. Carbohydrate addition can affect stability and cell recognition. Proteolytic cleavage converts inactive precursors into active products; insulin, for example, is produced through removal of peptide segments. Conjugated proteins also require non-polypeptide prosthetic groups, such as heme in hemoglobin.

Proteasomes degrade many damaged, misfolded or no-longer-needed proteins after they have been marked for destruction. Proteolysis prevents accumulation and releases amino acids for reuse. This recycling changes protein abundance independently of transcription. A cell's functional protein concentration is therefore the balance of transcription, RNA processing and decay, translation, maturation, transport and degradation.