4.8 Article

LINE-1 RNA splicing and influences on mammalian gene expression

Journal

NUCLEIC ACIDS RESEARCH
Volume 34, Issue 5, Pages 1512-1521

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkl027

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Funding

  1. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM045668] Funding Source: NIH RePORTER
  2. NIGMS NIH HHS [R01 GM045668, R01 GM45668] Funding Source: Medline

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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. L1 transcription is largely suppressed in most tissues, but L1 mRNA and/or proteins are still detectable in testes, a number of specific somatic cell types, and malignancies. Down-regulation of L1 expression via premature polyadenylation has been found to be 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 mRNAs can potentially contribute to expression ofopen reading frame 2-related products and therefore have implications for the mobility of SINEs even if 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.

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