retrotransposition

Retrotransposition is a molecular process by which an RNA transcript is reverse-transcribed into complementary DNA and inserted at a new genomic location. It can create intronless copies of genes, known as processed pseudogenes or retrogenes, and also spread noncoding elements such as SINEs. Retrotransposition operates through retrotransposons, genetic elements that move via an RNA intermediate.

Two main classes participate. Autonomous retrotransposons, such as LINEs (long interspersed nuclear elements), encode the proteins needed for reverse transcription and insertion, including reverse transcriptase and endonuclease. Non-autonomous elements, including SINEs (for example Alu) and SVA elements, lack their own machinery and rely on the enzymatic activity provided by LINEs to mobilize themselves.

Mechanistically, a gene’s mRNA is produced and exported to the cytoplasm. The LINE-encoded reverse transcriptase then copies the mRNA into cDNA, which is inserted back into the genome, often at a new site via endonuclease activity. The insertion typically generates target-site duplications and may retain a poly-A tail, while introns are absent because the transcript was already spliced. The resulting copies are usually intronless and may lack regulatory sequences.

Outcomes range from neutral to deleterious to advantageous. Most processed copies are nonfunctional pseudogenes, but some retrogenes can acquire promoters and become functional. The human genome contains thousands of processed pseudogenes and relies on LINE-1 activity for mobilization of SINEs and SVAs. Retrotransposition contributes to genome evolution, variability, and, in some cases, disease through insertional mutagenesis. Detection relies on features such as lack of introns, presence of a poly-A tail, and target-site duplications.