Detection of human interchromosomal trans-splicing in sequence databanks

Autor(es)

Herai, Roberto Hirochi ^[1] ; Beleza Yamagishi, Michel E. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Genet & Mol Biol, BR-13083862 Campinas, SP - Brazil

^[2] Brazilian Agr Res Corp, Agr Informat Subdiv, Appl Bioinformat Lab, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BRIEFINGS IN BIOINFORMATICS; v. 11, n. 2, p. 198-209, MAR 2010.
• Citações Web of Science: 25

Resumo

Trans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, `Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence?', we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation. (AU)

• Processo FAPESP: 08/02647-3 - Estudo de inverted repeats em genomas de mamíferos e plantas
• Beneficiário: Roberto Hirochi Herai
• Modalidade de apoio: Bolsas no Brasil - Doutorado