An important role for RUNX3 in human L1 transcription and retrotransposition

Nuo Yang, Lin Zhang, Yue Zhang, Haig H. Kazazian

Research output: Contribution to journalArticlepeer-review

Abstract

LINE-1s (long interspersed nuclear elements-1) are abundant non-LTR retrotransposons that comprise 17% of the human genome. The 5′ untranslated region (5′UTR) of human L1 (L1Hs) houses a poorly understood internal promoter. Here we report that mutations at a putative runt-domain transcription factor (RUNX) site (+83 to +101) in the 5′UTR decreased L1Hs transcription and retrotransposition in cell culture-based assays. Exogenous expression of RUNX3, but not the other two RUNX family members, RUNX1 and RUNX2, increased L1Hs transcription and retrotransposition, which were otherwise decreased by siRNAs targeting RUNX3 and a dominant negative RUNX. Furthermore, the specific interaction between RUNX3 and its binding site was demonstrated by an electrophoretic mobility shift assay (EMSA) using an antiRUNX3 antibody. Interestingly, RUNX3 may also regulate the antisense promoter activity of L1Hs 5′UTR via another putative RUNX site (+526 to +508), as revealed by site-directed mutations and exogenous expression of RUNX factors. Our results indicate an important role for RUNX3 in L1Hs retrotransposition as well as transcription from its 5′UTR in both sense and antisense directions, and they should contribute to our understanding of the mechanism underlying L1Hs retrotransposition and its impact on the expression of adjacent cellular genes.

Original languageEnglish (US)
Pages (from-to)4929-4940
Number of pages12
JournalNucleic acids research
Volume31
Issue number16
DOIs
StatePublished - Aug 15 2003

ASJC Scopus subject areas

  • Genetics

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