Multicistronic

Multicistronic refers to a transcript or genetic arrangement that encodes more than one protein product. In biology, most prokaryotic mRNAs are polycistronic, containing several open reading frames within a single transcript. These transcripts are commonly organized as operons, where transcriptional units are coexpressed and translation of downstream cistrons often relies on separate ribosome binding sites, allowing coordinated production of functionally related proteins. Eukaryotic mRNAs are typically monocistronic, encoding a single protein per transcript, but multicistronic expression can be engineered for research, biotechnology, and therapy.

Biotechnological strategies to achieve multicistronic expression in eukaryotes include internal ribosome entry sites (IRES), which recruit ribosomes to downstream cistrons; and 2A peptides, short viral sequences that cause ribosome skipping to yield multiple, separate proteins from one transcript. Other approaches include trans-splicing and naturally occurring mechanisms in some organisms, such as operon-like gene clusters with trans-spliced leaders. Each method has trade-offs: IRES elements can produce uneven expression levels between cistrons; 2A peptides generally provide near-equimolar expression but add short peptide tags to proteins; trans-splicing can be efficient but may be less predictable.

Applications of multicistronic constructs include studying protein complexes, reconstituting metabolic pathways, and delivering multiple therapeutic genes in gene therapy. In bacteria, polycistronic operons enable tight, coordinated control of related enzymes; in synthetic biology, designed multicistronic constructs allow synchronized expression of multiple components from a single promoter.