Processed Pseudogenes of Human Endogenous Retroviruses Generated by LINEs: Their Integration, Stability, and Distribution

Abstract

We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5Ј end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.

The human L1 promoter: Variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity

“…We generated three reporter constructs, derived from L1.3, for which the first 10 bp immediately upstream of the L1 start were replaced by the corresponding sequences present in L1C, The underlined sequence at the top is the previously reported HERV-W LTR consensus sequence, also termed LTR17. Previously reported HERV-W full-length pseudogenes (Costas 2002;Pavlicek et al 2002a) are exemplified. GenBank accession nos.…”

La capture d’enveloppe par les rétrovirus

“…Les événements de « capture » d'un gène env sont susceptibles de se produire par au moins trois mécanismes de recombinaison: après co-encapsidation de génomes rétroviraux hétéro-logues [40], par brassage intragénomique d'exons par les rétro-éléments [24,26] …”

“…Toutefois, les propriétés de la composante de surface SU permettent également d'envisager une parenté avec des gènes codant pour des ligands de récepteurs membranaires (immunoglobulines, cytokines…). Ces deux origines pourraient être conciliées dans le cadre de la formation d'Env par recombinaison stochastique de domaines distincts des protéines [22,23], tel que cela est décrit, par exemple, dans le mécanisme de brassage des exons [24][25][26]. La plus forte conservation, au sein des enveloppes rétrovirales, des séquences TM par rapport aux séquences SU, suggère une acquisition modulaire en deux temps, au moins [27].…”

Ancient Transposable Elements, Processed Pseudogenes, and Endogenous Retroviruses

“…Processed pseudogenes can be derived from alternatively spliced mRNAs (24,25,30), antisense transcripts (31), or mRNAs derived from other repetitive elements such as endogenous retroviruses (30,32,33). It seems that virtually any RNA including non-coding RNAs can be potentially retroposed by L1 elements.…”

“…Approximately 90% of HERV genomic elements are such solo LTRs (3). Full-length elements are mostly found in regions with low recombination rates, such as AT-rich regions or chromosome Y (3,30,90,92,93). Thus, the HERV distribution is strikingly different from the insertional pattern of exogenous retroviruses and mostly reflects post-insertional processes.…”