RNA-binding proteins (RBPs) are required for post-transcriptional gene regulation. There are predicted to be in excess of 1500 RBPs encoded in the human genome. Many of the proteins contain established RNA binding domains such as the RNA recognition motif (RRM), the heterogenous ribonucleoprotein (hnRNP) K-homology (KH) domain or the C3H1 zinc-finger (ZF) domain. Proteins that have well established RNA binding functions include the RNA methylation readers, writers, erasers and helicases, and the RNA binding subunits of the spliceosome. It is increasingly being recognised that many more proteins have the capacity to bind to RNA via emerging structural mechanisms. RBPs are involved regulating cellular RNA modifications (e.g., N⁶-methyladenosine, polyadenylation), splicing, localization, translation and decay [4]. Cancers, neurodegenerative diseases, metabolic and connective tissue disorders have all been associated with dysregulation of various RBPs. Pathological activity has promoted the search for small-molecule RBP modulators as novel therapeutics [1].

n.b. RBPs with catalytic activity will be curated within the Enzymes section of this resource, and those without known catalytic activity will be curated in this section.

1. Łasiñska I, Mackiewicz J. (2019) Integrins as A New Target for Cancer Treatment. Anticancer Agents Med Chem, 19 (5): 580-586. [PMID:30451118]

2. Baker JD, Uhrich RL, Strovas TJ, Saxton AD, Kraemer BC. (2020) Targeting Pathological Tau by Small Molecule Inhibition of the Poly(A):MSUT2 RNA-Protein Interaction. ACS Chem Neurosci, 11 (15): 2277-2285. [PMID:32589834]

3. Chen YF, Shen Y, Yan DF, Ghazala M, Scemama de Gialluly MA, Srinivasan R, Farrar AN, Friedrich RM, Adams DJ. (2024) Electrophile Determines Cellular Phenotypes among XPO1-Targeting Small Molecules. J Med Chem, 67 (14): 12033-12054. [PMID:39005064]

4. Dominguez D, Freese P, Alexis MS, Su A, Hochman M, Palden T, Bazile C, Lambert NJ, Van Nostrand EL, Pratt GA et al.. (2018) Sequence, Structure, and Context Preferences of Human RNA Binding Proteins. Mol Cell, 70 (5): 854-867.e9. [PMID:29883606]

5. Etchin J, Berezovskaya A, Conway AS, Galinsky IA, Stone RM, Baloglu E, Senapedis W, Landesman Y, Kauffman M, Shacham S et al.. (2017) KPT-8602, a second-generation inhibitor of XPO1-mediated nuclear export, is well tolerated and highly active against AML blasts and leukemia-initiating cells. Leukemia, 31 (1): 143-150. [PMID:27211268]

6. Faust TB, Yoon H, Nowak RP, Donovan KA, Li Z, Cai Q, Eleuteri NA, Zhang T, Gray NS, Fischer ES. (2020) Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat Chem Biol, 16 (1): 7-14. [PMID:31686031]

7. Hing ZA, Fung HY, Ranganathan P, Mitchell S, El-Gamal D, Woyach JA, Williams K, Goettl VM, Smith J, Yu X et al.. (2016) Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies. Leukemia, 30 (12): 2364-2372. [PMID:27323910]

8. Sandanayaka VP, Shacham S, Kauffman M, Schechter S, Mccauley D, Landesman Y, Senapedis W, Saint-Martin J-R. (2013) Nuclear transport modulators and uses thereof. Patent number: WO2013019561A1. Assignee: Karyopharm Therapeutics, Inc.. Priority date: 29/07/2011. Publication date: 04/07/2013.

9. Vercruysse T, De Bie J, Neggers JE, Jacquemyn M, Vanstreels E, Schmid-Burgk JL, Hornung V, Baloglu E, Landesman Y, Senapedis W et al.. (2017) The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia. Clin Cancer Res, 23 (10): 2528-2541. [PMID:27780859]