AU-rich elements(AREs) and their binding proteins coordinate developmental programs

doi:10.16352/j.issn.1001-6325.2026.07.0982

Abstract

Abstract: Objective To explore the potential synergistic roles of AU-rich elements (AREs) and their binding proteins (AREBPs) in post-transcriptional regulation and the translation process. Methods A customized algorithm was utilized to extract the core ARE motifs within the 3'UTR regions across human and mouse genomes.The binding sites of AREBPs were identified by integrating data from the Postar3 database, public CLIP-seq datasets from GEO.Independently constructed CLIP-seq database and PrismNet deep learning predictions. Fisher's exact test was applied to calculate the enrichment degree (odds ratio) of specific AREBPs in tissue-specific genes.The co-expression patterns between AREBPs and target genes were analyzed by combining the GTEx database and tissue-specific developmental RNA-seq datasets (e.g., kidney development dataset GSE100859). Results A comprehensive genome-wide map of conserved 3'UTR AREs in humans and mice was successfully generated.Specific AREBPs exhibited significant binding enrichment (P＜0.05) in tissue-specific genes associated with muscle, brain, kidney and heart.Expression profiling analysis revealed that during tissue development (such as kidney development), genes containing AREs showed significantly different expression patterns compared to those without AREs. Conclusions AREs and their binding proteins play a highly specific function in kidney development, genes containing AREs showed significantly different expression patterns as compared to those without AREs. Conclusions AREs and their binding proteins play a highly specific role in post-transcriptional regulation across different tissues. This study provides a crucial bioinformatics evidence for understanding the RNA regulatory mechanisms underlying tissue development and homeostasis maintenance.

Key words: enhanced UV crosslinking immunoprecipitation-sequencing(eCLIP-seq), AU-rich elements(AREs), tissue develop-ment, RNA-binding proteins, multi-omics, database

CLC Number:

Q811.4

XIN Mingjun, HUO Yue, WANG Fang. AU-rich elements(AREs) and their binding proteins coordinate developmental programs[J]. Basic & Clinical Medicine, 2026, 46(7): 982-989.

References

[1] Vasudevan S,Steitz JA. AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2[J]. Cell,2007,128:1105-1118.
[2] Bakheet T, Frevel M, Williams BR, et al. ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins[J]. Nucleic Acids Res, 2001, 29: 246-254.
[3] Sandler H, Kreth J, Timmers HT, et al. Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin[J]. Nucleic Acids Res, 2011, 39: 4373-4386.
[4] Mukherjee N, Corcoran DL, Nusbaum JD, et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability[J]. Mol Cell, 2011, 43: 327-339.
[5] Van Nostrand EL, Pratt GA, Shishkin AA, et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP)[J]. Nat Methods, 2016, 13: 508-514.
[6] Zhao W, Zhang S, Zhu Y, et al. POSTAR3: an updated platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins[J].Nucleic Acids Res, 2022,50:D287-D294.doi:10.1093/nar/gkab702
[7] Xu Y, Zhu J, Huang W, et al. PrismNet: predicting protein-RNA interaction using in vivo RNA structural information[J].Nucleic Acids Res, 2023,51:W468-W477.doi:10.1093/nar/gkad353
[8] Spasic M, Friedel CC, Schott J, et al. Genome-wide assessment of AU-rich elements by the AREScore algorithm[J].PLoS Genet,2012,8:e1002433.doi:10.1371/journal.pgen.1002433.
[9] Chi B, Öztürk MM, Paraggio CL, et al. Causal ALS genes impact the MHC class Ⅱ antigen presentation pathway[J].Proc Natl Acad Sci USA, 2023,120:e2305756120. doi:10.1073/pnas.2305756120
[10] Lessel D, Zeitler DM, Reijnders MRF, et al. Germline AGO2 mutations impair RNA interference and human neurological development[J].Nat Commun, 2020,11:5797.doi:10.1038/s41467-020-19572-5
[11] Sullivan WJ, Mullen PJ, Schmid EW, et al. Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization[J].Cell, 2018,175:117-132.
[12] Abbadi D, Yang M, Chenette DM, et al. Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs[J].Proc Natl Acad Sci USA, 2019,116:11285-11290.