Graziano Pesole*, Sabino Liuni 1, Giorgio Grillo 1, Flavio Licciulli 2, Flavio Mignone, Carmela Gissi and Cecilia Saccone 2
Dipartimento di Fisiologia e Biochimica Generali, Università
di Milano, via Celoria 26, 20133 Milano, Italy,
1 Centro di Studio sui Mitocondri e Metabolismo Energetico
del Consiglio Nazionale delle Ricerche (CNR), via Amendola 165/A, 70126
Bari, Italy and
2 Dipartimento di Biochimica e Biologia Molecolare, Università
di Bari, via Orabona 4, 70126 Bari, Italy
* To whom correspondence should be addressed. Tel: +39 02 58354915;
Fax +39 02 58354912;
Email: graziano.pesole@unimi.it
The 5'- and 3'-untranslated regions (5'- and 3'-UTRs) of eukaryotic
mRNAs are known to play a crucial role in post-transcriptional regulation
of gene expression modulating nucleo-cytoplasmic mRNA transport, translation
efficiency, subcellular localization and stability. UTRdb is a specialized
database of 5' and 3' untranslated sequences of eukaryotic mRNAs cleaned
from redundancy. UTRdb entries are enriched with specialized information
not present in the primary databases including the presence of nucleotide
sequence patterns already demonstrated by experimental analysis to have
some functional role. All these patterns have been collected in the UTRsite
database so that it is possible to search any input sequence for the presence
of annotated functional motifs. Furthermore, UTRdb entries have been annotated
for the presence of repetitive elements. All Internet resources we implemented
for retrieval and functional analysis of 5'- and 3'-UTRs of eukaryotic
mRNAs are accessible at http://bighost.area.ba.cnr.it/BIG/UTRHome/
The completion of the sequencing of human and of other organism genomes
has opened new avenues for understanding the basic mechanisms of cell function.
These processes mostly rely on a spatial–temporal coordinated expression
of genes mediated by regulatory elements embedded in the non-coding part
of the
genomes. Among non-coding regions, the 5'- and 3'-untranslated regions
(5'- and 3'-UTRs) of eukaryotic mRNAs have often been experimentally demonstrated
to contain sequence elements crucial for many aspects of gene regulation
and expression (1–7).
The main functional roles so far demonstrated for 5'- and 3'-UTR sequences are: (i) control of mRNA cellular and subcellular localization (4, 7–9); (ii) control of mRNA stability (1, 10, 11); (iii) control of mRNA translation efficiency (12–14).
Several regulatory signals have already been identified in 5'- or 3'-UTR sequences, usually corresponding to short oligonucleotide tracts, also able to fold in specific secondary structures, which are protein binding sites for various regulatory proteins.
The analysis of large collections of functionally equivalent sequences (15, 16), such as 5'- and 3'-UTR sequences, could indeed be very useful for defining their structural and compositional features as well as for searching the alleged function-associated sequence patterns (17–19). For this reason we constructed UTRdb, a specialized sequence collection, deprived from redundancy, of 5'- and 3'-UTR sequences from eukaryotic mRNAs.
UTRdb entries have been enriched with specialized information, not present in the primary databases, including the presence of sequence patterns demonstrated by experimental evidence to play some functional role. Additionally, because 10% of mammalian mRNAs contain repetitive elements in their UTRs (20) but they are usually not annotated in the original records, we decided to add this information into our database as well.
We also created UTRsite, a collection of functional sequence patterns
located in the 5'- or 3'-UTR sequences which could prove very useful for
automatic annotation of anonymous sequences generated by sequencing projects
as well as for finding previously undetected signals in known gene sequences.
...
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