Gene regulation by sense-antisense overlap of polyadenylation signals.

We show here that expression of genes from convergent transcription units can be regulated by the formation of double-stranded RNA (dsRNA) in the region of overlapping polyadenylation signals. The model system employed is the mouse polyomavirus. The early and late genes of polyomavirus are transcribed from opposite strands of the circular viral genome.

Alu element-mediated gene silencing.

The Alu elements are conserved approximately 300-nucleotide-long repeat sequences that belong to the SINE family of retrotransposons found abundantly in primate genomes. Pairs of inverted Alu repeats in RNA can form duplex structures that lead to hyperediting by the ADAR enzymes, and at least 333 human genes contain such repeats in their 3'-UTRs. Here, we show that a pair of inverted Alus placed within the 3'-UTR of egfp reporter mRNA strongly represses EGFP expression, whereas a single Alu has little or no effect.

Retention and repression: fates of hyperedited RNAs in the nucleus.

Double-stranded RNA (dsRNA) is often formed in the nuclei of mammalian cells, but in this compartment it does not induce the effects characteristic of cytoplasmic dsRNA. Rather, recent work has suggested that nuclear dsRNA is a target for the ADAR class of enzymes, which deaminate adenosines to inosines. Further, there are a number of distinct fates of such edited RNA, including nuclear retention and perhaps also gene silencing.

SINEs point to abundant editing in the human genome.

Recent bioinformatic analyses suggest that almost all human transcripts are edited by adenosine deaminases (ADARs), converting adenosines to inosines. Most of this editing is in Alu element transcripts, which are unique to primates. This editing might have no function or might be involved in functions such as the regulation of splicing, chromatin or nuclear localization of transcripts.

A GC-box within the proximal promoter region of the rat cathepsin L gene activates transcription in Sertoli cells of sexually mature rats.

It has been proposed that stage-specific gene expression in Sertoli cells results from sequential activation and repression of transcription. However, the exact molecular mechanisms are unknown. As a first step in addressing this fundamental issue, we recently demonstrated that a 3-kilobase (kb) genomic fragment immediately upstream of the rat cathepsin L translation start site directed stage-specific expression of a reporter gene only in Sertoli cells of transgenic mice in a manner comparable to that of the endogenous gene (predominantly in stages VI-VIII tubules).