Long Interspersed Nuclear Element-1 (LINE-1) is an autonomous retrotransposon that generates new genomic insertions through the retrotransposition of a RNA intermediate. Expression of LINE-1 is tightly repressed in most somatic tissues to prevent DNA damage and ensure genomic integrity. However, the reactivation of LINE-1 has been documented in cancer and the role of LINE-1 protein expression and retrotransposition has become of interest in the development, progression, and adaptation of many epithelial neoplasms, including prostate cancer. Here, we examined endogenous LINE-1 protein expression and localization in a panel of prostate cancer cells and observed a diverse range of LINE-1 expression patterns between cell lines. Subcellular localization of LINE-1 proteins, ORF1p and ORF2p, revealed distinct expression patterns. ORF1p, a nucleic acid chaperone that binds LINE-1 mRNA, was predominantly expressed in the cytoplasm, with minor localization in the nucleus. ORF2p, containing endonuclease and reverse transcriptase domains, exhibited punctate foci in the nucleus and also displayed co-localization with PCNA and γH2AX. Using a retrotransposition reporter assay, we found variations in LINE-1 retrotransposition between cell lines. Overall, our findings reveal new insight into the expression and retrotransposition of LINE-1 in prostate cancer. The prostate cancer cells we investigated provide a unique model for investigating endogenous LINE-1 activity and provide a functional model for studying LINE-1 mechanisms in prostate cancer.

Spermatozoa of virtually all species can spontaneously take up exogenous DNA or RNA molecules and internalize them into nuclei. In this article I review evidence for a key role of a reverse transcriptase (RT) activity, encoded by LINE-1 retrotransposons, in the fate of the internalized nucleic acid molecules and their implication in transgenerational inheritance. LINE-1-derived RT, present in sperm heads, can reverse-transcribe the internalized molecules in cDNA copies: exogenous RNA is reverse-transcribed in a one-step reaction, whereas DNA is first transcribed into RNA and subsequently reverse-transcribed. Both RNA and cDNA molecules can be delivered from sperm cells to oocytes at fertilization, further propagated throughout embryogenesis and inherited in a non-Mendelian fashion in tissues of adult animals. The reverse-transcribed sequences are extrachromosomal, low-abundance, and mosaic distributed in tissues of adult individuals, where they are variably expressed. These “retrogenes” are transcriptionally competent and induce novel phenotypic traits in animals. Growing evidence indicate that cancer tissues produce DNA- and RNA-containing exosomes. We recently found that these exosomes are released in the bloodstream and eventually taken up into epididymal spermatozoa, consistent with the emerging view that a transgenerational flow of extrachromosomal RNA connects soma to germline and, further, to next generation embryos. Spermatozoa play a crucial bridging role in this process: they act as collectors of somatic information and as delivering vectors to the next generation. On the whole, this phenomenon is compatible with a Lamarckian-type view and closely resembles Darwinian pangenesis.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Ilaria Sciamanna 1 , Alberto Gualtieri 1 , Pier Vincenzo Piazza 2 , Corrado Spadafora 1 1 Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy 2 NeuroCentre Magendie, INSERM U862, Univ Bdx2, Bordeaux, France Correspondence to: Corrado Spadafora, e-mail: cspadaf@tin.it Keywords: Retrotransposon, reverse transcriptase, inhibitor, non coding RNA, cancer therapy Received: August 01, 2014 Accepted: September 16, 2014 Published: October 29, 2014 ABSTRACT LINE-1 retrotransposons encode the reverse transcriptase (RT) enzyme, required for their own mobility, the expression of which is inhibited in differentiated tissues while being active in tumors. Experimental evidence indicate that the inhibition of LINE-1-derived RT restores differentiation in cancer cells, inhibits tumor progression and yields globally reprogrammed transcription profiles. Newly emerging data suggest that LINE-1-encoded RT modulates the biogenesis of miRNAs, by governing the balance between the production of regulatory double-stranded RNAs and RNA:DNA hybrid molecules, with a direct impact on global gene expression. Abnormally high RT activity unbalances the transcriptome in cancer cells, while RT inhibition restores ‘normal’ miRNA profiles and their regulatory networks. This RT-dependent mechanism can target the myriad of transcripts - both coding and non-coding, sense and antisense - in eukaryotic transcriptomes, with a profound impact on cell fates. LINE-1-encoded RT emerges therefore as a key regulator of a previously unrecognized mechanism in tumorigenesis

An increasing body of data are revealing key roles of epigenetics in evolutionary processes. The scope of this manuscript is to assemble in a coherent frame experimental evidence supporting a role of epigenetic factors and networks, active during embryogenesis, in orchestrating variation-inducing phenomena underlying evolution, seen as a global process. This process unfolds over two crucial levels: i) a flow of RNA-based information - predominantly small regulatory RNAs released from somatic cells exposed to environmental stimuli - taken up by spermatozoa and delivered to oocytes at fertilization and ii) the highly permissive and variation-prone environments offered by zygotes and totipotent early embryos. Totipotent embryos provide a variety of biological tools favouring the emergence of evolutionarily significant phenotypic novelties driven by RNA information. Under this light, neither random genomic mutations, nor the sieving role of natural selection are required, as the sperm-delivered RNA cargo conveys specific information and acts as "phenotypic-inducer" of defined environmentally acquired traits.