Since the discovery that genes are split into intron and exons, the studies of the mechanisms involved in splicing pointed to presence of consensus signals in an attempt to generalize the process for all living cells. However, as discussed in the present review, splicing is a theme full of variations. The trans-splicing of pre-mRNAs, the joining of exons from distinct transcripts, is one of these variations with broad distribution in the phylogenetic tree. The biological meaning of this phenomenon is discussed encompassing reactions resembling a possible noise to mechanisms of gene expression regulation. All of them however, can contribute to the generation of life diversity.Key words: RNA processing -alternative trans-splicing -spliced leader RNA -trypanosomatids -nematodes -mammalian Most of the protein-coding eukaryotic genes display an interrupted structure alternating exons and introns. After transcription, introns must be removed from the primary transcript (pre-mRNA) to generate a translatable mature mRNA. It is interesting to note that the mature mRNA is constituted of 5' and 3' untranslatable regions (UTR) flanking the open reading frame (ORF) and that UTR are also exons. The precise excision of the introns and the joining of neighboring exons is a complex process generally named splicing, and when this processing occurs within a single pre-mRNA molecule it can also be called cis-splicing (Moore et al. 1993, Burge et al. 1999.Cis-splicing occurs in a two-step mechanism, each step consisting of a transesterification reaction (Moore et al. 1993) (Fig. 1A). The spliceosome, a ribonucleoprotein machinery composed of five small ribonucleoproteins (U1, U2, U4, U5, U6 snRNPs, named in relation to the kind of associated RNA molecule) and approximately 300 distinct proteins, is responsible for the splicing catalysis (Burge et al. 1999).Much effort was expended on the comprehension of the structure and dynamics of this complex machine during the splicing process, but the rules that discriminate introns and exons within the message are still poorly understood. Nevertheless, four conserved pre-mRNA sequence elements, which interact with the spliceosome, have been characterized as determinants in the splicing process (Moore et al. 1993, Burge et al. 1999 (Fig. 1C). In mammals, the 5' splice site consensus is AG/GURAGU (R for purine, /for splice site, bold for the dinucleotide 5' intron boundary) while the 3' splice site consensus is YAG/G (Y for pyrimidine, /for splice site, bold for the dinucleotides 3' intron boundary). There is also a conservation of nucleotide sequence around the branch point, CURAY (Y for pyrimidine, R for purine and A for branch Recently, other cis-regulatory elements were implicated in splice site recognition, e.g. the exonic splicing enhancers (ESEs) (Fig. 1C). ESEs are localized within exons and interact with a family of proteins rich in serine and arginine (SR proteins) that recruits the spliceosome to the proximal splice site .Although the presence of those consensuses was observed, it i...