Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

Abstract

LINE-1 are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of eukaryotes via germline transposition, with up to 100 000 copies in mammalian genomes. LINE-1 elements transpose by reverse transcription of their own transcript. Transposition requires synthesis of a full-length, sense-strand transcripts and proteins encoded by open reading frame (ORF) 1 and ORF2. Although severely repressed in most normal tissues, LINE-1 occasionally leads to disease by insertional mutagenesis. In the present study, Northern blot and in situ hybridization analyses revealed a template-strand transcription of LINE-1 ORF2 (encoding reverse transcriptase, RT) in lymphoid organs and the liver from MRL-+/+ and Fas-deficient MRL/lpr strains and their normal ancestors. While these sense transcripts are restricted to the nucleus in hepatocytes, they are also found in the cytoplasm in splenocytes. In contrast to transcription, ORF2 translation was detected only in MRL strains, as shown by the cytoplasmic labelling of splenic cells obtained with a monoclonal antibody recognizing the LINE-1 RT. This antibody coprecipitated two proteins of 45 and 12 kDa from MRL/lpr lymphoid organ lysates that were removed by pretreatment with anti-b2-microglobulin antiserum, suggesting a structural association between a LINE-1 product and a major histocompatibility complex class I or class I-like molecule.

Mice Deficient for a Small Cluster of Piwi-Interacting RNAs Implicate Piwi-Interacting RNAs in Transposon Control1

“…3A). As previously reported for L1 hybridizations with adult mouse testis RNA [32,33], a ;7-kb mRNA was detected (Fig. 3A, arrow).…”

“…ORF1 protein is expressed at low levels in several somatic and germ cell types in the testes of adult mice [32,33]. Although transposition may occur in any cell type, expression in meiotic stage germ cells concomitant with strand breakage during recombination would allow L1 insertion into new chromosomal locations.…”

Arsenic trioxide: a promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice

“…[9][10][11] However, lpr mutation cannot account for the entire autoimmune syndrome of MRL/lpr mice and other genes of pathologic importance in the MRL background have been mapped. 12,13 MRL/lpr mice spontaneously develop a lupuslike syndrome that can affect many organs. The murine cutaneous lesions resemble human discoid lupus erythematosus.…”

B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lprmice

“…However, lpr mutation cannot account for the entire autoimmune syndrome of MRL/lpr mice, and other genes of pathologic importance in the MRL background have been mapped [17,18].…”