7SHX

A functional SNP regulates E-cadherin expression by dynamically remodeling the 3D structure of a promoter-associated non-coding RNA transcript, NMR, minimized average structure

Summary for 7SHX

• Entry DOI: 10.2210/pdb7shx/pdb
• NMR Information: BMRB: 51127
• Descriptor: RNA (94-MER) (1 entity in total)
• Functional Keywords: parna, snp, rna
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 30487.21

Authors

Sharma, S.,Varani, G. (deposition date: 2021-10-11, release date: 2022-10-19, Last modification date: 2024-05-15)

Primary citation

Sharma, S.,Pisignano, G.,Merulla, J.,Catapano, C.V.,Varani, G.
A functional SNP regulates E-cadherin expression by dynamically remodeling the 3D structure of a promoter-associated non-coding RNA transcript.
Nucleic Acids Res., 50:11331-11343, 2022

PubMed Abstract: Transcription of E-cadherin, a tumor suppressor that plays critical roles in cell adhesion and the epithelial-mesenchymal transition, is regulated by a promoter-associated non-coding RNA (paRNA). The sense-oriented paRNA (S-paRNA) includes a functional C/A single nucleotide polymorphism (SNP rs16260). The A-allele leads to decreased transcriptional activity and increased prostate cancer risk. The polymorphic site is known to affect binding of a microRNA-guided Argonaute 1 (AGO1) complex and recruitment of chromatin-modifying enzymes to silence the promoter. Yet the SNP is distant from the microRNA-AGO1 binding domain in both primary sequence and secondary structure, raising the question of how regulation occurs. Here we report the 3D NMR structure of the 104-nucleotide domain of the S-paRNA that encompasses the SNP and the microRNA-binding site. We show that the A to C change alters the locally dynamic and metastable structure of the S-paRNA, revealing how the single nucleotide mutation regulates the E-cadherin promoter through its effect on the non-coding RNA structure.

PubMed: 36243981
DOI: 10.1093/nar/gkac875

Experimental method

SOLUTION NMR