The identification and functional annotation of RNA structures conserved in vertebrates

Area of Science:

• Genomics and Bioinformatics
• Molecular Biology
• RNA Structure and Function

Background:

• Conserved RNA structures (CRSs) play crucial roles in RNA stabilization, localization, and protein interactions.
• Conservation across species suggests fundamental functional importance of these RNA structures.

Purpose of the Study:

• To computationally screen vertebrate genomes for conserved RNA structures (CRSs) using structure-based alignments.
• To identify and characterize novel functional RNA elements and their regulatory roles.

Main Methods:

• Computational screening of vertebrate genomes for CRSs, prioritizing structure-based over sequence-based alignments.
• Correction for sequence identity and GC content to refine CRS predictions.
• Experimental validation using CaptureSeq, qRT-PCR, and in vitro RNA structure probing.

Main Results:

• Prediction of approximately 516,000 human genomic regions containing CRSs.
• Significant overlap of human-mouse CRS regions with RNA binding protein (RBP) binding sites and tissue-specific transcription.
• Identification of 662 novel CRS regions in human fetal brain, with experimental validation of shared structure and expression for selected pairs.

Conclusions:

• CRSs are prevalent in the human genome and associated with functional RNA elements.
• Structured enhancer RNAs and extended 3' ends exhibit increased expression levels.
• The findings support the RNA-mediated functionality of transcribed, uncharacterized regulatory regions containing CRSs.