7.15: Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1 elements (LINE) and the Alu elements (SINE).
Transposition is typically a chance occurrence, which means the location where the transposable element is inserted is random. Transposons that are randomly inserted into genes can interfere with gene expression and cause genetic dysfunctions. A classic example is the insertion of the L1 retrotransposon into the factor VIII gene that causes hemophilia. L1 integration in the tumor suppressor gene Adenomatous polyposis coli (APC) has also been found in colon cancer patients. The SINE element Alu causes chromosomal aberrations and also has been linked to congenital defects like neurofibromatosis.
The cellular mechanism for repression of retrotransposons involves chemical modifications such as methylation of LINE elements or producing truncated retrotransposons. The vast majority of LINE and SINE elements in the human genome are truncated at their 5’ end due to erroneous reverse transcription. Such retrotransposons are usually silent, meaning they do not affect gene expression after insertion.
The occurrence of retrotransposons in cancerous cells has been exploited to develop retrotransposons like L1, as cancer biomarkers. It has been observed that methylation of L1 is significantly reduced in cancerous cells. This type of hypomethylation leads to genomic instability. Hypomethylated L1 levels have been investigated as biomarkers for malignancies like breast, colon, and skin cancer.