LINE1

Genetic structure of murine LINE1 and SINEs. Bottom: proposed structure of L1 RNA-protein (RNP) complexes. ORF1 proteins form trimers, exhibiting RNA binding and nucleic acid chaperone activity.

LINE1 (also L1 and LINE-1) are transposable elements in the DNA of some organisms and belong to the group of Long interspersed nuclear elements (LINEs). L1 comprise approximately 17% of the human genome.[1]

The majority of L1 in the human genome are inactive; however, some retained the ability to retrotranspose.[2] Human L1 has been reported to have transferred to the genome of the gonorrhea bacteria.[3]

Structure

A typical L1 element is approximately 6,000 base pairs long and consists of two non-overlapping open reading frames (ORF) which are flanked by UTR and target site duplications. In humans, ORF2 is thought to be translated by an unconventional termination/reinitiation mechanism,[4] while mouse L1s contain an internal ribosome entry site (IRES) upstream of each ORF.[5]

5' UTR

The 5' Untranslated region (UTR) of the L1 element contains a strong, internal RNA Polymerase II transcription promoter in sense[6]

The 5' UTR of mouse L1s contain a variable number of GC-rich tandemly repeated monomers of around 200bp, followed by a short non-monomeric region.

Human 5’UTRs are ~900bp in length and do not contain repeated motifs. All families of human L1s harbor in their most 5’ extremity a binding motif for the transcription factor YY1.[7] Younger families have also two binding sites for SOX-family transcription factors, and both YY1 and SOX sites were shown to be required for human L1 transcription initiation and activation.[8][9]

Both mouse and human 5’UTRs contain as well a weak antisense promoter of unknown function[10][11]

ORF1

The first ORF encode a 500 amino acid - 40kDa protein that lacks homology with any protein of known function. In vertebrates, it contains a conserved C-terminus domain and a highly variable coiled-coil N-terminus that mediates the formation of ORF1 trimetric complexes. ORF1 trimers have RNA-binding and nucleic acid chaperone activity that are necessary for retrotransposition.[12]

ORF2

The second ORF of L1 encodes a protein that has endonuclease and reverse transcriptase activity. The encoded protein has a molecular weight of 150 kDA.

See also

  • L1Base, a database of functional annotations & predictions of active LINE1 elements

References

  1. ↑ International Human Genome Sequencing Consortium (Feb 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi:10.1038/35057062. PMID 11237011.
  2. ↑ Ostertag, Eric M.; Kazazian Jr, Haig H. (December 2001). "Biology of Mammalian L1 Retrotransposons". Annual Review of Genetics. 35 (1): 501–538. doi:10.1146/annurev.genet.35.102401.091032.
  3. ↑ Yong, Ed (2011-02-16). "Gonorrhea has picked up human DNA (and that's just the beginning)". National Geographic. Retrieved 2016-07-14.
  4. ↑ Alisch, Reid S.; Garcia-Perez, Jose L.; Muotri, Alysson R.; Gage, Fred H.; Moran, John V. (2006-01-15). "Unconventional translation of mammalian LINE-1 retrotransposons". Genes & Development. 20 (2): 210–224. doi:10.1101/gad.1380406. ISSN 0890-9369. PMC 1356112. PMID 16418485.
  5. ↑ Li, Patrick Wai-Lun; Li, Jinfang; Timmerman, Stephanie L.; Krushel, Les A.; Martin, Sandra L. (2006-01-01). "The dicistronic RNA from the mouse LINE-1 retrotransposon contains an internal ribosome entry site upstream of each ORF: implications for retrotransposition". Nucleic Acids Research. 34 (3): 853–864. doi:10.1093/nar/gkj490. ISSN 0305-1048.
  6. ↑ Swergold, G. D. (1990). "Identification, characterization, and cell specificity of a human LINE-1 promoter". Molecular and Cellular Biology. 10 (12): 6718–6729. doi:10.1128/MCB.10.12.6718. PMC 362950. PMID 1701022.
  7. ↑ Becker, K. G.; Swergold, G. D.; Ozato, K.; Thayer, R. E. (October 1993). "Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element". Human Molecular Genetics. 2 (10): 1697–1702. doi:10.1093/hmg/2.10.1697. ISSN 0964-6906. PMID 8268924.
  8. ↑ Tchénio, Thierry; Casella, Jean-François; Heidmann, Thierry (2000-01-15). "Members of the SRY family regulate the human LINE retrotransposons". Nucleic Acids Research. 28 (2): 411–415. doi:10.1093/nar/28.2.411. ISSN 0305-1048.
  9. ↑ Athanikar, Jyoti N.; Badge, Richard M.; Moran, John V. (2004-01-01). "A YY1-binding site is required for accurate human LINE-1 transcription initiation". Nucleic Acids Research. 32 (13): 3846–3855. doi:10.1093/nar/gkh698. ISSN 0305-1048.
  10. ↑ Li, Jingfeng; Kannan, Manoj; Trivett, Anna L.; Liao, Hongling; Wu, Xiaolin; Akagi, Keiko; Symer, David E. (2014-04-01). "An antisense promoter in mouse L1 retrotransposon open reading frame-1 initiates expression of diverse fusion transcripts and limits retrotransposition". Nucleic Acids Research. 42 (7): 4546–4562. doi:10.1093/nar/gku091. ISSN 0305-1048.
  11. ↑ Mätlik, K; Redik, K; Speek, M (2006). "L1 antisense promoter drives tissue-specific transcription of human genes". Journal of Biomedicine and Biotechnology. 2006 (1): 71753. doi:10.1155/JBB/2006/71753. PMC 1559930. PMID 16877819.
  12. ↑ Martin, Sandra L. (2006). "The ORF1 Protein Encoded by LINE-1: Structure and Function During L1 Retrotransposition". Journal of Biomedicine and Biotechnology. 2006: 1–6. doi:10.1155/jbb/2006/45621. ISSN 1110-7243.
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