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Review
. 2025 Jul 19;17(14):2367.
doi: 10.3390/nu17142367.

Orchestrating Nutrient Homeostasis: RNA-Binding Proteins as Molecular Conductors in Metabolic Disease Pathogenesis

Siyuan Sun  1 , Xinchun Li  1 , Jianan Zhai  1 , Chenxu Lu  1 , Weiru Yu  1 , Wenhao Wu  1 , Juan Chen  1
Affiliations
Review

Orchestrating Nutrient Homeostasis: RNA-Binding Proteins as Molecular Conductors in Metabolic Disease Pathogenesis

Siyuan Sun et al. Nutrients. .

Abstract

RNA-binding proteins (RBPs) are critical regulators of post-transcriptional processes, playing essential roles in nutrient metabolism and metabolic homeostasis. This literature review explores how RBPs influence the metabolism of glucose, lipid, and amino acid metabolism by controlling processes like mRNA stability and translation regulation. The dysregulation of RBPs, including HuR, PTB, and YTHDF1, is linked to metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease. Advances in techniques like TREX technology and transcriptome analysis have deepened our understanding of RBP functions. Additionally, RBPs show promise as potential biomarkers and targets for new therapies. Future research directions in RBPs could focus on tissue-specific regulation and nutrient-RBP interactions. This could pave the way for more personalized treatments and improved metabolic health.

Keywords: LACE-seq; RNA-binding protein; diabetes; nutrients; obesity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Different RNA-binding proteins categorized by domains and their binding models (RBP: RNA-binding proteins; RRM: RNA recognition motif; CSD: cold shock domains; KH: K homology domain; ZnF: zinc finger motif).
Figure 2
Figure 2
The participation of RBPs in different processes of nutrient metabolism. (A) A1CF participates in fructose metabolism through alternative splicing of mRNAs in hepatocytes. (B) FTO promotes triglyceride accumulation by m6A demethylation of mRNAs. (C) ARID5A regulates adipocyte differentiation via mRNA 3′ untranslated region stabilization. (TAG: triacylglycerol; A1CF: APOBEC1 complementation factor; FTO: fat mass and obesity-associated protein; m6A: N6-methyladenosine; Atg: autophagy-related protein; YTHDF2: YTH N6-methyladenosine RNA-binding protein F2; ARID5A: AT-rich interaction domain 5A; IL6: interleukin 6; Ox40: TNF receptor superfamily member 4; Ppar-γ2: peroxisome proliferators-activated receptor gamma 2).
Figure 3
Figure 3
Advanced technologies in discovering the characteristics of RBPs. (A) Perturb Sequencing (Perturb-seq). (B) Targeted RNase H-mediated extraction (TREX) technology. (C) Linear Amplification of Complementary DNA Ends and Sequencing (LACE-seq). (D) Captured RNA in situ conformation sequencing (CRIC-seq).
Figure 4
Figure 4
Future directions in RNA-binding protein research in nutrient metabolism.
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