RNA m⁶A modification orchestrates a LINE-1-host interaction that facilitates retrotransposition and contributes to long gene vulnerability.

ABSTRACT: The molecular basis underlying the interaction between retrotransposable elements (RTEs) and the human genome remains poorly understood. Here, we profiled N⁶-methyladenosine (m⁶A) deposition on nascent RNAs in human cells by developing a new method MINT-Seq, which revealed that many classes of RTE RNAs, particularly intronic LINE-1s (L1s), are strongly methylated. These m⁶A-marked intronic L1s (MILs) are evolutionarily young, sense-oriented to hosting genes, and are bound by a dozen RNA binding proteins (RBPs) that are putative novel readers of m⁶A-modified RNAs, including a nuclear matrix protein SAFB. Notably, m⁶A positively controls the expression of both autonomous L1s and co-transcribed L1 relics, promoting L1 retrotransposition.

SUBMITTER: Xiong F 

PROVIDER: S-EPMC8324889 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature