Mining small RNA structure elements in untranslated regions of human and mouse mRNAs using structure-based alignment

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Untranslated Regions (UTRs) of messenger RNAs (mRNAs) contain regulatory elements impacting mRNA metabolism, including localization, translation, and stability.
• Known RNA stem-loop structures in UTRs, such as the histone 3' UTR stem-loop structure (HSL3) and iron response element (IRE), are conserved in mammalian orthologs and found in genes within shared biological pathways.
• The prevalence of such conserved RNA structures across all mammalian UTRs remains largely unexplored.

Purpose of the Study:

• To systematically identify conserved small RNA stem-loop structures within mammalian UTRs.
• To determine if these structures are associated with genes sharing common biological functions (Gene Ontology terms).

Main Methods:

• Development and application of a systematic computational approach named GLEAN-UTR.
• Analysis of conserved RNA stem-loop structures between human and mouse orthologs.
• Association of identified structures with genes possessing common Gene Ontology terms.

Main Results:

• The GLEAN-UTR approach identified 90 distinct RNA structure groups, encompassing 748 individual structures.
• The known HSL3 and IRE structures were among the top hits, validating the method's effectiveness based on structural conservation.
• The findings suggest a broader existence of conserved stem-loop structures in mammalian UTRs than previously recognized.

Conclusions:

• Mammalian UTRs likely harbor numerous conserved stem-loop structures.
• These structures may play a significant role in the coordinated post-transcriptional regulation of genes involved in common biological pathways.