STRUCTURAL AND COMPOSITIONAL ANALYSIS OF TRANSCRIPTION START SITES AND 5’-UNTRANSLATED REGIONS IN HUMAN MRNAS

Graziano Pesole
Dipartimento di Fisiologia e Biochimica
Generali
Università di Milano
via Celoria, 26
20133 Milano
Italy
telephone: +39-02-58354915
fax: +39-02-58354912
email: graziano.pesole@unimi.it
prestype: Platform
presenter: Graziano Pesole

Pesole G.*, Gissi C.*, Grillo G.§, Licciulli F.§, Mignone F.*, Iacono M.*, Liuni S.§
* Università di Milano, Milan, Italy (graziano.pesole@unimi.it)
§ CSMME-C.N.R., Bari, Italy

The 5’ and 3’ untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA nucleo-cytoplasmic transport, subcellular localization, stability and translation efficiency. In order to study the general structural and compositional features of these sequences we have previously developed UTRdb, a specialized database of 5’ and 3’ UTR sequences of eukaryotic mRNAs cleaned from redundancy (Pesole et al. 2000a).

Utrdb (release 15.0) contains about 250,000 entries (>65,000,000 nucleotides) which are also annotated for the presence of functional sequence patterns whose biological activity has been experimentally demonstrated. All these patterns have been collected in the UTRsite database where for each functional pattern, corresponding to a specific entry, the consensus structure is reported with a short description of its biological activity and the relevant bibliography.

All Web resources we implemented for the retrieval and the analysis of UTR sequences are available at the UTR home page (http://bighost.area.ba.cnr.it/BIG/UTRHome/) we recently implemented. UTRdb entries can be retrieved through the SRS system where crosslinks to UTRsite as well as to the nucleotide or aminoacid primary database are also established. Through the Web facility UTRscan any input sequence can be searched for the presence of a functional pattern annotated in UTRsite and UTRblast allows to assess sequence similarity between a query sequence and UTRdb entries.

The analysis of complete UTR sequences contained in this database allowed us to define specific structural and compositional features of UTRs from mRNAs belonging to various eukaryotic taxa (Pesole et al. 2000b).

We now report some recent results obtained by analyzing the oligonucleotide context and the compositional features of the transcription start site for those human genes where the full length 5’UTR as well as the corresponding genomic region was available. Furthermore, we investigated the presence and features of upstream ORFs, of sequence tracts similar or complementary to 18S rRNA and the context of initiator ATG (Pesole et al. 2000c), which are known to affect the mRNA translation efficiency.

Pesole, G., S. Liuni, G. Grillo, F. Licciulli, A. Larizza et al., 2000a UTRdb and UTRsite: specialized databases of sequences and functional elements of 5' and 3' untranslated regions of eukaryotic mRNAs. Nucleic Acids Res 28: 193-196.

Pesole, G., C. Gissi, G. Grillo, F. Licciulli, S. Liuni et al., 2000b Analysis of oligonucleotide AUG start codon context in eukariotic mRNAs. Gene 261: 85-91.

Pesole, G., G. Grillo, A. Larizza and S. Liuni, 2000c The untranslated regions of eukaryotic mRNAs: structure, function and bioinformatic tools for their analysis. Briefings in Bioinformatics 1: 236-249.