# SLFN11 Restricts LINE-1 Mobility

## TL;DR

SLFN11, a protein in the Schlafen family, restricts LINE-1 transposon activity by blocking its transcription and promoting epigenetic silencing.

## Contribution

SLFN11 is newly identified as a LINE-1 restriction factor that acts through RNA binding and epigenetic mechanisms.

## Key findings

- SLFN11 inhibits LINE-1 retrotransposition via its helicase domain.
- SLFN11 binds to the LINE-1 5′UTR and prevents RNA polymerase II recruitment.
- SLFN11 promotes heterochromatinization, indicating an epigenetic suppression pathway.

## Abstract

Long interspersed element-1 (LINE-1) is the only active autonomous transposon comprising about 17% of human genomes. LINE-1 transposition can cause the mutation and rearrangement of the host’s genomic DNA. The host has, therefore, developed multiple mechanisms to restrict LINE-1 mobility. Here, we report that SLFN11, a member of the Schlafen family, can restrict LINE-1 retrotransposition, and the inhibitory activity requires its helicase domain. Mechanistically, SLFN11 specifically binds to the LINE-1 5′ untranslated region (5′UTR) and blocks RNA polymerase II recruitment, thereby suppressing its transcription. Furthermore, SLFN11 promotes heterochromatinization, suggesting an epigenetic inhibition pathway.