[miRNAs and cancer].

Contrary to current belief, the concept of microRNA (miRNA) is quite old. Indeed, the first report on a small RNA able to control the translation of a specific messenger RNA (and therefore called translational control RNA or tcRNA) dates 35-year back. miRNAs waited until 1993 to be "rediscovered" and become the focus of an intense research activity which led to the discovery of several hundreds of them, to the unraveling of their biosynthesis and of their involvement in numerous physiological and pathological processes, notably in cancer.

[Genetic predisposition to prostate cancer].

The advent and recent use of Genome-Wide Association studies (GWAS) for the search of genetic predisposition markers for prostate cancer since 2006 has put a very strong emphasis on the 8q24 locus where several single nucleotide polymorphisms (SNP) have been significantly associated with an increased relative risk. A wealth of recent papers have all confirmed the interest of this locus and identified several others. Interestingly, these markers seem to have additive effects pointing to the high complexity of prostate cancer predisposition.

[RNA and cancer].

The aim of this review is to draw the attention to the numerous steps of gene expression which operate at the RNA level and which are significant drivers of the transformation process. The analysis of genomic abnormalities was at first limited to gross chromosomal alterations and to DNA point mutations. Then came the era of transciptomes which were originally believed, since they were mRNAs, to be a faithful reflection of the expressed proteins.

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16) that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles.

[Alternative splicing: a novel pharmacological target with wide therapeutic potential].

Alternative splicing is a process by which a single stretch of genomic DNA yields several mRNAs encoding different proteins. Once believed to be a marginal phenomenon, alternative splicing now appears to be widespread among higher organisms and to be behind a large repertoire of human diseases. It involves a flexible mechanism for selecting splice sites, based on regulatory sequences recognized by cognate trans-acting protein factors (stimulatory SR proteins, or their antagonists).

The spliceosome: a novel multi-faceted target for therapy.

The spliceosome is a dynamic and flexible ribonucleoprotein enzyme that removes intronic sequences in a regulated manner. Spliceosome action enables one stretch of genomic DNA sequence to yield several mRNAs that encode different proteins. It depends on a flexible mechanism for selecting splice sites, which calls for regulatory sequences (splicing enhancers or silencers) recognized by cognate trans-acting protein factors and constitutive ribonucleoprotein devices to build up the catalytic core.

Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors.

The prevalence of alternative splicing as a target for alterations leading to human genetic disorders makes it highly relevant for therapy. Here we have used in vitro splicing reactions with different splicing reporter constructs to screen 4,000 chemical compounds for their ability to selectively inhibit spliceosome assembly and splicing. We discovered indole derivatives as potent inhibitors of the splicing reaction.

Spontaneous apoptosis in the intra-ductal component's stroma of breast invasive carcinoma.

Spontaneous apoptosis by in situ detection of DNA fragmentation (DNAf) was investigated in breast invasive ductal carcinoma (IDC) frozen samples removed from 61 untreated patients. The incidence of DNAf was low in carcinoma cells and was mainly detected in the stroma. In the stroma at a distance from carcinoma cells, DNAf was inversely related to estradiol plasma level variations (p=0.

[From genomics to post-genomics: back to the origins?].

The purpose of this review is to emphasize the multiplicity and importance, physiological and pathological, of gene regulation levels which operate after the initiation step of transcription. Albeit crucial, this step is only the first one of a long cascade of events which eventually end up in the selection of functional messengers appropriate to the nature of the cells and to their immediate needs. Throughout this long pathway, of which only a few steps will be mentioned here, this review will attempt to address the central role played by RNA, not only as a substrate but as an actor of its own regulation.