Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons

Guillermo Banuelos-Sanchez, Laura Sanchez, Maria Benitez-Guijarro, Valentin Sanchez-Carnerero, Carmen Salvador-Palomeque, Pablo Tristan-Ramos, Meriem Benkaddour-Boumzaouad, Santiago Morell, Jose L Garcia-Puche, Sara R Heras, Francisco Franco-Montalban, Juan A Tamayo, Jose L Garcia-Perez

Research output: Contribution to journalArticlepeer-review

Abstract

Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice. LTR- and LINE-1-retroelements use different mechanisms for retrotransposition, although both involve the reverse transcription of an intermediate retroelement-derived RNA. Retrotransposon activity continues to effect the germline and somatic genomes, generating interindividual variability over evolution and potentially influencing cancer and brain physiology, respectively. However, relatively little is known about the functional consequences of retrotransposition. In this study, we have synthesized and characterized reverse transcriptase inhibitors specific for mammalian LINE-1 retrotransposons, which might help deciphering the functional impact of retrotransposition in vivo.

Original languageEnglish
Pages (from-to)1095-1109.e14
JournalCell Chemical Biology
Volume26
Issue number8
Early online date30 May 2019
DOIs
Publication statusPublished - 15 Aug 2019

Keywords

  • Cell Line
  • Dideoxynucleosides/chemical synthesis
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Long Interspersed Nucleotide Elements/drug effects
  • Molecular Structure
  • Reverse Transcriptase Inhibitors/chemical synthesis

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