Marco Stefani | PubMed Health

PubMed2006

MoD Tools: regulatory motif discovery in nucleotide sequences from co-regulated or homologous genes.

Understanding the complex mechanisms regulating gene expression at the transcriptional and post-transcriptional levels is one of the greatest challenges of the post-genomic era. The MoD (MOtif Discovery) Tools web server comprises a set of tools for the discovery of novel conserved sequence and structure motifs in nucleotide sequences, motifs that in turn are good candidates for regulatory activity. The server includes the following programs: Weeder, for the discovery of conserved transcription factor binding sites (TFBSs) in nucleotide sequences from co-regulated genes; WeederH, for the discovery of conserved TFBSs and distal regulatory modules in sequences from homologous genes; RNAProfile, for the discovery of conserved secondary structure motifs in unaligned RNA sequences whose secondary structure is not known. In this way, a given gene can be compared with other co-regulated genes or with its homologs, or its mRNA can be analyzed for conserved motifs regulating its post-transcriptional fate. The web server thus provides researchers with different strategies and methods to investigate the regulation of gene expression, at both the transcriptional and post-transcriptional levels. Available at http://www.pesolelab.it/modtools/ and http://www.beacon.unimi.it/modtools/.

Binding Sites↗

PubMed2004

RNAProfile: an algorithm for finding conserved secondary structure motifs in unaligned RNA sequences.

The recent interest sparked due to the discovery of a variety of functions for non-coding RNA molecules has highlighted the need for suitable tools for the analysis and the comparison of RNA sequences. Many trans-acting non-coding RNA genes and cis-acting RNA regulatory elements present motifs, conserved both in structure and sequence, that can be hardly detected by primary sequence analysis alone. We present an algorithm that takes as input a set of unaligned RNA sequences expected to share a common motif, and outputs the regions that are most conserved throughout the sequences, according to a similarity measure that takes into account both the sequence of the regions and the secondary structure they can form according to base-pairing and thermodynamic rules. Only a single parameter is needed as input, which denotes the number of distinct hairpins the motif has to contain. No further constraints on the size, number and position of the single elements comprising the motif are required. The algorithm can be split into two parts: first, it extracts from each input sequence a set of candidate regions whose predicted optimal secondary structure contains the number of hairpins given as input. Then, the regions selected are compared with each other to find the groups of most similar ones, formed by a region taken from each sequence. To avoid exhaustive enumeration of the search space and to reduce the execution time, a greedy heuristic is introduced for this task. We present different experiments, which show that the algorithm is capable of characterizing and discovering known regulatory motifs in mRNA like the iron responsive element (IRE) and selenocysteine insertion sequence (SECIS) stem-loop structures. We also show how it can be applied to corrupted datasets in which a motif does not appear in all the input sequences, as well as to the discovery of more complex motifs in the non-coding RNA.

3' Untranslated Regions↗