AN ACTIVELY RETROTRANSPOSING, NOVEL SUBFAMILY OF MOUSE L1 ELEMENTS

Retrotransposition of LINEs and other retroelements increases repetiti on in mammalian genomes and can cause deleterious mutations, Recent in sertions of two full-length L1s, L1(spa) and L1(Orl), caused the disea se phenotypes of the spastic and Orleans reeler mice respectively. Her e we show that these two recently retrotransposed L1s are nearly ident ical in sequence, have two open reading frames and belong to a novel s ubfamily related to the ancient F subfamily. We have named this new su bfamily T-F (for transposable) and show that many full-length members of this family are present in the mouse genome. The T-F 5' untranslate d region has promoter activity, and T-F-type RNA is abundant in cytopl asmic ribonucleoprotein particles, which are likely intermediates in r etrotransposition. Both L1(spa) and L1(Orl) have reverse transcriptase activity in a yeast-based assay and retrotranspose at high frequency in cultured cells, Together, our data indicate that the T-F subfamily of L1s contains a major class of mobile elements that is expanding in the mouse genome.