Abstract
In this report, using the database of RNA-binding protein specificities (RBPDB) and our previously published RNA-seq data, we analyzed the interactions between RNA and RNA-binding proteins to decipher the role of alternative splicing in metabolic disorders induced by TNF-α. We identified 13 395 unique RNA-RBP interactions, including 385 unique RNA motifs and 35 RBPs, some of which (including MBNL-1 and 3, ZFP36, ZRANB2, and SNRPA) are transcriptionally regulated by TNF-α. In addition to some previously reported RBPs, such as RBMX and HuR/ELAVL1, we found a few novel RBPs, such as ZRANB2 and SNRPA, to be involved in the regulation of metabolic syndrome-associated genes that contain an enrichment of tetrameric RNA sequences (AUUU). Taken together, this study paves the way for novel RNA-protein interaction-based therapeutics for treating metabolic syndromes.
Keywords:
RNA-RBP interaction; RNA-binding proteins; TNF-α; alternative splicing; bioinformatics analysis; metabolic syndromes.
© 2021 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing / drug effects*
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Base Sequence
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Computational Biology / methods
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ELAV-Like Protein 2 / genetics
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ELAV-Like Protein 2 / metabolism
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Genome-Wide Association Study
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HEK293 Cells
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Heterogeneous-Nuclear Ribonucleoprotein K / genetics
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Heterogeneous-Nuclear Ribonucleoprotein K / metabolism
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Humans
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Metabolic Syndrome / genetics*
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Metabolic Syndrome / metabolism
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Metabolic Syndrome / pathology
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Protein Binding
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RNA / genetics
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RNA / metabolism
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Ribonucleoprotein, U1 Small Nuclear / genetics*
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Ribonucleoprotein, U1 Small Nuclear / metabolism
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Tristetraprolin / genetics
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Tristetraprolin / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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ELAV-Like Protein 2
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ELAVL2 protein, human
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Heterogeneous-Nuclear Ribonucleoprotein K
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MBNL1 protein, human
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MBNL3 protein, human
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RNA-Binding Proteins
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Ribonucleoprotein, U1 Small Nuclear
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Tristetraprolin
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Tumor Necrosis Factor-alpha
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U1A protein
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ZFP36 protein, human
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ZRANB2 protein, human
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HNRNPK protein, human
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RNA