LINE-1 RNA splicing and influences on mammalian gene expression

摘要

Long interspersed element-1 elements compose on average one-fifth of mammalian genomes. The expression and retrotransposition of L1 is restricted by a number of cellular mechanisms in order to limit their damage in both germ-line and somatic cells. L1transcription is largely suppressed in most tissues, but L1 mRNA and/or proteins are still detectable in testes, a number of specific somatic ceil types, and malignancies. Down-regulation of L1 expression via premature polyadenyiation has been found tobe a secondary mechanism of limiting L1 expression. We demonstrate that mammalian L1 elements contain numerous functional splice donor and acceptor sites. Efficient usage of some of these sites results in extensive and complex splicing of L1. Several splice variants of both the human and mouse L1 elements undergo retrotransposition. Some of the spliced L1 mRMAs can potentially contribute to expression of open reading frame 2-related products and therefore have implications for the mobility of SiNEs evenif they are incompetent for L1 retrotransposition. Analysis of the human EST database revealed that L1 elements also participate in splicing events with other genes. Such contribution of functional splice sites by L1 may result in disruption of normal gene expression or formation of alternative mRNA transcripts.