Functional classification of long non-coding RNAs by k-mer content
Autor: | Megan D. Schertzer, Allison R Baker, Daniel Sprague, Qidi Chen, Jessime M. Kirk, Peter J. Mucha, Kevin M. Weeks, David W Collins, J. Mauro Calabrese, Joshua Wooten, Matthew J. Smola, Kaoru Inoue, David M Lee, Shuo Wang, Christopher R Horning, Susan O Kim |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Sequence analysis Sequence alignment Computational biology Biology Article Homology (biology) Conserved sequence Mice 03 medical and health sciences 0302 clinical medicine Databases Genetic Genetics Animals Cluster Analysis Humans Nucleotide Motifs Conserved Sequence Base Sequence Sequence Analysis RNA RNA Molecular Sequence Annotation Hep G2 Cells 030104 developmental biology Potassium Channels Voltage-Gated k-mer Nucleic Acid Conformation RNA Long Noncoding K562 Cells Sequence motif Sequence Alignment Algorithms 030217 neurology & neurosurgery |
Zdroj: | Nature genetics |
ISSN: | 1546-1718 1061-4036 |
DOI: | 10.1038/s41588-018-0207-8 |
Popis: | The functions of most long non-coding RNAs (lncRNAs) are unknown. In contrast to proteins, lncRNAs with similar functions often lack linear sequence homology; thus, the identification of function in one lncRNA rarely informs the identification of function in others. We developed a sequence comparison method to deconstruct linear sequence relationships in lncRNAs and evaluate similarity based on the abundance of short motifs called k-mers. We found that lncRNAs of related function often had similar k-mer profiles despite lacking linear homology, and that k-mer profiles correlated with protein binding to lncRNAs and with their subcellular localization. Using a novel assay to quantify Xist-like regulatory potential, we directly demonstrated that evolutionarily unrelated lncRNAs can encode similar function through different spatial arrangements of related sequence motifs. K-mer-based classification is a powerful approach to detect recurrent relationships between sequence and function in lncRNAs. |
Databáze: | OpenAIRE |
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