Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions

TL;DR

This paper introduces two statistical methods for analyzing mammalian 3' UTR sequences to identify potential regulatory elements, including miRNA binding sites, by examining oligonucleotide frequency patterns.

Contribution

The paper presents novel complementary approaches for detecting regulatory sequences in 3' UTRs based on oligonucleotide overrepresentation and strand asymmetry analysis.

Findings

Identified known miRNA seed regions in 3' UTRs

Proposed new candidate regulatory sequences for experimental testing

Methods effectively detect conserved and strand-biased oligonucleotides

Abstract

3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.