Jasmine Jacob‐Hirsch

RNA molecules transmit the information encoded in the genome and generally reflect its content. Adenosine-to-inosine (A-to-I) RNA editing by ADAR proteins converts a genomically encoded adenosine into inosine. It is known that most RNA editing in human takes place in the primate-specific Alu sequences, but the extent of this phenomenon and its effect on transcriptome diversity are not yet clear. Here, we analyzed large-scale RNA-seq data and detected ∼1.6 million editing sites. As detection sensitivity increases with sequencing coverage, we performed ultradeep sequencing of selected Alu sequences and showed that the scope of editing is much larger than anticipated. We found that virtually all adenosines within Alu repeats that form double-stranded RNA undergo A-to-I editing, although most sites exhibit editing at only low levels (<1%). Moreover, using high coverage sequencing, we observed editing of transcripts resulting from residual antisense expression, doubling the number of edited sites in the human genome. Based on bioinformatic analyses and deep targeted sequencing, we estimate that there are over 100 million human Alu RNA editing sites, located in the majority of human genes. These findings set the stage for exploring how this primate-specific massive diversification of the transcriptome is utilized.

Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas.