AGO-RBP Crosstalk on Target MRNAs: Implications in MiRNA-guided Gene Silencing and Cancer

Overview

Journal Transl Oncol

Specialty Oncology

Date 2022 Apr 27

PMID 35477066

Authors

Pavan Kumar Kakumani

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) are important regulators of mRNA translation and stability in eukaryotes. While miRNAs can only bind their target mRNAs in association with Argonaute proteins (AGOs), RBPs directly bind their targets either as single entities or in complex with other RBPs to control mRNA metabolism. miRNA binding in 3' untranslated regions (3' UTRs) of mRNAs facilitates an intricate network of interactions between miRNA-AGO and RBPs, thus determining the fate of overlapping targets. Here, we review the current knowledge on the interplay between miRNA-AGO and multiple RBPs in different cellular contexts, the rules underlying their synergism and antagonism on target mRNAs, as well as highlight the implications of these regulatory modules in cancer initiation and progression.

Citing Articles

Integrated Analysis of microRNA Targets Reveals New Insights into Transcriptional-Post-Transcriptional Regulatory Cross-Talk.

Panni S, Pizzolotto R Biology (Basel). 2025; 14(1).

PMID: 39857274 PMC: 11762646. DOI: 10.3390/biology14010043.

RNA Binding Proteins as Potential Therapeutic Targets in Colorectal Cancer.

Singh V, Singh A, Liu A, Fuchs S, Sharma A, Spiegelman V Cancers (Basel). 2024; 16(20).

PMID: 39456596 PMC: 11506615. DOI: 10.3390/cancers16203502.

Regulatory role of RNA-binding proteins in microRNA biogenesis.

Hynes C, Kakumani P Front Mol Biosci. 2024; 11:1374843.

PMID: 38567098 PMC: 10985210. DOI: 10.3389/fmolb.2024.1374843.

Experimental capture of miRNA targetomes: disease-specific 3'UTR library-based miRNA targetomics for Parkinson's disease.

Hart M, Kern F, Fecher-Trost C, Krammes L, Aparicio E, Engel A Exp Mol Med. 2024; 56(4):935-945.

PMID: 38556547 PMC: 11059366. DOI: 10.1038/s12276-024-01202-5.

The miRNA-target interactions: An underestimated intricacy.

Diener C, Keller A, Meese E Nucleic Acids Res. 2023; 52(4):1544-1557.

PMID: 38033323 PMC: 10899768. DOI: 10.1093/nar/gkad1142.

References

Sternburg E, Estep J, Nguyen D, Li Y, Karginov F . Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs. Sci Rep. 2018; 8(1):15316. PMC: 6192998. DOI: 10.1038/s41598-018-33596-4. View

Fu R, Olsen M, Webb K, Bennett E, Lykke-Andersen J . Recruitment of the 4EHP-GYF2 cap-binding complex to tetraproline motifs of tristetraprolin promotes repression and degradation of mRNAs with AU-rich elements. RNA. 2016; 22(3):373-82. PMC: 4748815. DOI: 10.1261/rna.054833.115. View

Lederer M, Bley N, Schleifer C, Huttelmaier S . The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer. Semin Cancer Biol. 2014; 29:3-12. DOI: 10.1016/j.semcancer.2014.07.006. View

Ji J, Ding K, Luo T, Xu R, Zhang X, Huang B . PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1. Oncogene. 2019; 39(5):1125-1139. PMC: 6989403. DOI: 10.1038/s41388-019-1050-9. View

Masamha C, Xia Z, Yang J, Albrecht T, Li M, Shyu A . CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature. 2014; 510(7505):412-6. PMC: 4128630. DOI: 10.1038/nature13261. View

Ehses J, Fernandez-Moya S, Schroger L, Kiebler M . Synergistic regulation of mRNA by HuR and miR-26/RISC in neurons. RNA Biol. 2020; 18(7):988-998. PMC: 8216180. DOI: 10.1080/15476286.2020.1795409. View

Kedde M, Van Kouwenhove M, Zwart W, Vrielink J, Elkon R, Agami R . A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility. Nat Cell Biol. 2010; 12(10):1014-20. DOI: 10.1038/ncb2105. View

Muller S, Bley N, Glass M, Busch B, Rousseau V, Misiak D . IGF2BP1 enhances an aggressive tumor cell phenotype by impairing miRNA-directed downregulation of oncogenic factors. Nucleic Acids Res. 2018; 46(12):6285-6303. PMC: 6158595. DOI: 10.1093/nar/gky229. View

Nam J, Rissland O, Koppstein D, Abreu-Goodger C, Jan C, Agarwal V . Global analyses of the effect of different cellular contexts on microRNA targeting. Mol Cell. 2014; 53(6):1031-1043. PMC: 4062300. DOI: 10.1016/j.molcel.2014.02.013. View

10.

Olson P, Lu J, Zhang H, Shai A, Chun M, Wang Y . MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev. 2009; 23(18):2152-65. PMC: 2751988. DOI: 10.1101/gad.1820109. View

11.

Jafarifar F, Yao P, Eswarappa S, Fox P . Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L. EMBO J. 2011; 30(7):1324-34. PMC: 3094116. DOI: 10.1038/emboj.2011.38. View

12.

Brennan S, Kuwano Y, Alkharouf N, Blackshear P, Gorospe M, Wilson G . The mRNA-destabilizing protein tristetraprolin is suppressed in many cancers, altering tumorigenic phenotypes and patient prognosis. Cancer Res. 2009; 69(12):5168-76. PMC: 2724875. DOI: 10.1158/0008-5472.CAN-08-4238. View

13.

Kedde M, Strasser M, Boldajipour B, Vrielink J, Slanchev K, le Sage C . RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell. 2007; 131(7):1273-86. DOI: 10.1016/j.cell.2007.11.034. View

14.

Vasilyev N, Polonskaia A, Darnell J, Darnell R, Patel D, Serganov A . Crystal structure reveals specific recognition of a G-quadruplex RNA by a β-turn in the RGG motif of FMRP. Proc Natl Acad Sci U S A. 2015; 112(39):E5391-400. PMC: 4593078. DOI: 10.1073/pnas.1515737112. View

15.

Sternburg E, Karginov F . Global Approaches in Studying RNA-Binding Protein Interaction Networks. Trends Biochem Sci. 2020; 45(7):593-603. DOI: 10.1016/j.tibs.2020.03.005. View

16.

Smits M, Wurdinger T, van Het Hof B, Drexhage J, Geerts D, Wesseling P . Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB J. 2012; 26(6):2639-47. DOI: 10.1096/fj.11-202820. View

17.

Ajdukovic J . HIF-1--a big chapter in the cancer tale. Exp Oncol. 2016; 38(1):9-12. View

18.

Tien J, Chugh S, Goodrum A, Cheng Y, Mannan R, Zhang Y . AGO2 promotes tumor progression in KRAS-driven mouse models of non-small cell lung cancer. Proc Natl Acad Sci U S A. 2021; 118(20). PMC: 8157917. DOI: 10.1073/pnas.2026104118. View

19.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

20.

Sanchez-Tillo E, Siles L, de Barrios O, Cuatrecasas M, Vaquero E, Castells A . Expanding roles of ZEB factors in tumorigenesis and tumor progression. Am J Cancer Res. 2011; 1(7):897-912. PMC: 3196287. View