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| Author(s): |
Rodrigo Louro
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2006-11-27 |
| Examining board members: |
Sergio Verjovski de Almeida;
Marcelo Ribeiro da Silva Briones;
Enilza Maria Espreafico;
Suely Lopes Gomes;
Vilma Regina Martins
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| Advisor: | Sergio Verjovski de Almeida |
| Abstract | |
With the completion of the human genome sequence, attention has shifted towards determining the complete set of human transcripts. Multiple lines of evidence suggest that while only a small fraction of protein-coding mRNAs remains to be described, there is a huge amount of uncharacterized non-coding RNAs (ncRNAs). In this context, the present work sought to explore the gene expression information provided by ESTs to identify and characterize new human transcripts. A genomic-wide search for cancer related gene family members identified novel small GTPase genes, and highlighted an uncharacterized subfamily that may have a tumor suppressor role in prostate cancer. A class of long unspliced ncRNAs, expressed antisense from introns of protein-coding genes was described using custom-designed microarray platforms enriched with unannotated sequences. The expression profile of 23 intronic ncRNAs was significantly correlated to the degree of prostate tumor differentiation (Gleason Score), and could be used as a candidate prognostic molecular maker. A total of 39 intronic ncRNAs were responsive to androgen stimulation, poiting to a mechanism of intronic expression regulation by physiological hormone signals. Intronic ncRNA biogenesis seems to be complex, since a fraction of them is not transcribed by RNA Polymerase II. Intronic transcription was correlated to exon usage in androgen treated cells. Tissue expression signatures of intronic transcription were conserved in human and mouse, and intronic transcripts were found to interact with regulatory proteins. This work provides new and original contributions that support the postulated role of ncRNAs in the fine tunning of the human transcriptional program. (AU) | |