readthroughs

Readthroughs are events in gene expression in which an established boundary is bypassed, allowing information to be read or translated beyond its usual limit. The term is used most often in two contexts: stop codon readthrough during translation and transcriptional readthrough by RNA polymerase II.

Stop codon readthrough occurs when the ribosome fails to terminate at a stop codon and continues translation to a downstream stop, producing an extended protein isoform. This process is influenced by the identity of the stop codon, the nucleotides surrounding it, RNA structures, and the availability of termination factors. Readthrough can be regulated to generate functional protein variants with extended C-termini, and it is exploited by some viruses to expand their coding capacity. In cellular genes, regulated readthrough contributes to proteome diversity and can affect localization, stability, and activity of the resulting proteins. Detection methods include ribosome profiling and mass spectrometry to identify extended products.

Transcriptional readthrough refers to the continuation of transcription beyond the canonical termination signal, producing transcripts that extend past the end of a gene. This can yield longer 3' untranslated regions, readthrough transcripts, or chimeric RNAs, and is influenced by termination signals, chromatin context, and cellular conditions such as stress. Readthrough transcripts can affect RNA stability, localization, and translation, and may contribute to regulatory networks or disease states. Detection typically relies on RNA sequencing approaches, including long-read sequencing, and specialized 3' end mapping techniques.

Together, readthroughs contribute to molecular diversity and regulatory complexity in cells, with ongoing relevance to understanding gene expression and potential therapeutic applications. See also stop codon readthrough and transcriptional termination.